ALG12-congenital disorder of glycosylation

Mendelian MONDO:0011783 Pathograph 28 Show in embeddings browser congenital disorder of glycosylation type I disorder of protein N-glycosylation

ALG12-congenital disorder of glycosylation is a rare autosomal recessive disorder of protein N-linked glycosylation caused by biallelic ALG12 variants. Loss of ALG12 mannosyltransferase activity disrupts N-glycan-precursor formation, produces a type I congenital disorder of glycosylation biochemical pattern, and causes variable neurodevelopmental, immune, coagulation, growth, skeletal, cardiac, and prenatal manifestations.

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1
Inheritance
9
Pathophys.
14
Phenotypes
3
Hypotheses
28
Pathograph
1
Genes
1
Medical Actions
1
Trials
10
References
1
Deep Research
👪

Inheritance

1
Autosomal recessive inheritance HP:0000007
ALG12-CDG is an autosomal recessive condition caused by biallelic pathogenic ALG12 variants.
Autosomal recessive inheritance
Show evidence (2 references)
PMID:38717015 SUPPORT Human Clinical
"ALG12-CDG specifically is caused by biallelic pathogenic variants in ALG12."
The 2024 prenatal case report directly states biallelic ALG12 causation.
CGGV:assertion_21631e85-8133-4703-a77c-c046effb6e56-2023-02-15T200000.000Z SUPPORT Other
"ALG12 | HGNC:19358 | ALG12-congenital disorder of glycosylation | MONDO:0011783 | AR | Definitive"
ClinGen classifies the ALG12-ALG12-CDG relationship as definitive with autosomal recessive inheritance.
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Mechanistic Hypotheses

3
Canonical ALG12-CDG Glycoprotein Hypoglycosylation Model
canonical_alg12_cdg_model CANONICAL
Evidence balance 1 support
Biallelic loss of ALG12 function reduces the ER alpha1,6-mannosyltransferase step in lipid-linked oligosaccharide assembly. The resulting precursor defect causes underoccupancy and abnormal N-glycosylation of multiple proteins and a multisystem CDG phenotype. The biochemical sequence is canonical, while the tissue-specific intermediates connecting systemic glycoprotein dysfunction to individual clinical findings remain unresolved.
Pathograph links
ALG12 mannosyltransferase deficiency -> N-glycan precursor formation defect DIRECT Loss of ALG12 alpha1,6-mannosyltransferase activity blocks addition of the eighth mannose to the dolichol-linked GlcNAc2Man7 intermediate, impairing completion of the N-glycan precursor used for transfer to proteins.
N-glycan precursor formation defect -> Abnormal serum and IgG N-glycosylation INDIRECT KNOWN INTERMEDIATES The precursor-assembly defect alters N-glycosylation-site occupancy and downstream glycan processing, producing abnormal total-serum and IgG N-glycan profiles; the intervening transfer and processing steps make this an indirect biochemical link. Intermediates: Transfer of incomplete lipid-linked oligosaccharides, reduced protein N-glycosylation-site occupancy, and downstream glycan processing.
N-glycan precursor formation defect -> Multisystem glycoprotein dysfunction INDIRECT UNKNOWN INTERMEDIATES Reduced N-glycosylation-site occupancy and abnormal glycan processing disrupt the folding, trafficking, and function of many glycoproteins, producing systemic dysfunction through incompletely resolved protein- and tissue-specific intermediates.
Multisystem glycoprotein dysfunction -> Neurodevelopmental and brain involvement INDIRECT UNKNOWN INTERMEDIATES Multisystem glycoprotein dysfunction is associated with neurologic and brain manifestations, but the affected glycoproteins and intervening developmental pathways are unresolved.
Multisystem glycoprotein dysfunction -> Growth and feeding impairment INDIRECT UNKNOWN INTERMEDIATES Multisystem ALG12-CDG is associated with impaired growth and feeding; the glycoprotein and tissue-specific intermediates are unresolved.
Multisystem glycoprotein dysfunction -> Dysmorphic and genitourinary developmental involvement INDIRECT UNKNOWN INTERMEDIATES Multisystem ALG12-CDG is associated with craniofacial dysmorphism and male genital hypoplasia through unresolved developmental intermediates.
Abnormal serum and IgG N-glycosylation -> Decreased circulating immunoglobulin concentration UNKNOWN Abnormal IgG N-glycosylation and low serum immunoglobulins co-occur in ALG12-CDG, but the evidence does not establish that the glycan-profile abnormality directly causes the decreased concentration.
Abnormal serum and IgG N-glycosylation -> Recurrent infections UNKNOWN Recurrent infections co-occur with low immunoglobulins and abnormal IgG glycosylation, but the evidence does not establish a causal path from the measured glycan abnormality to infection susceptibility.
Abnormal serum and IgG N-glycosylation -> Abnormality of coagulation INDIRECT KNOWN INTERMEDIATES Hypoglycosylation and deficiency of factor XI provide a known protein-level intermediate linking systemic glycosylation abnormalities to an abnormal coagulation phenotype. Intermediates: Hypoglycosylation and deficiency of coagulation factor XI.
Neurodevelopmental and brain involvement -> Global developmental delay INDIRECT UNKNOWN INTERMEDIATES Developmental delay is part of the reported ALG12-CDG neurologic spectrum.
Neurodevelopmental and brain involvement -> Intellectual disability INDIRECT UNKNOWN INTERMEDIATES Intellectual disability is part of the reported ALG12-CDG neurologic spectrum.
Neurodevelopmental and brain involvement -> Hypotonia INDIRECT UNKNOWN INTERMEDIATES Hypotonia is part of the reported ALG12-CDG neurologic spectrum.
Growth and feeding impairment -> Failure to thrive INDIRECT UNKNOWN INTERMEDIATES Failure to thrive is a reported growth manifestation of ALG12-CDG.
Growth and feeding impairment -> Short stature INDIRECT UNKNOWN INTERMEDIATES Short stature is a reported growth manifestation of ALG12-CDG.
Dysmorphic and genitourinary developmental involvement -> Facial dysmorphism INDIRECT UNKNOWN INTERMEDIATES Dysmorphic features include craniofacial involvement.
Dysmorphic and genitourinary developmental involvement -> Hypoplastic male external genitalia INDIRECT UNKNOWN INTERMEDIATES Male genital hypoplasia is a genitourinary developmental manifestation.
Show evidence (1 reference)
PMID:12217961 SUPPORT In Vitro
"In the patient's fibroblasts, the biosynthetic intermediate GlcNAc(2)Man(7) oligosaccharide was detected both on the lipid carrier dolichyl pyrophosphate and on newly synthesized glycoproteins, thus pointing to a defect in the dolichyl pyrophosphate-GlcNAc(2)Man(7)-dependent ALG12 alpha1,6..."
Patient-fibroblast measurements directly support the ALG12 precursor-assembly defect at the center of the canonical model.
Severe Prenatal Renal-Skeletal Extension Model
severe_prenatal_renal_skeletal_model EMERGING
Evidence balance 2 support
A rare severe prenatal or neonatal branch may extend ALG12-CDG to multicystic renal malformation and skeletal-dysplasia-like abnormalities. This branch is kept separate from the canonical clinical spectrum because it is supported by limited severe-case evidence and its organ-specific intermediates are unknown.
Pathograph links
Multisystem glycoprotein dysfunction -> Renal and skeletal developmental involvement INDIRECT UNKNOWN INTERMEDIATES Rare severe prenatal or neonatal reports associate ALG12-CDG with renal and skeletal developmental abnormalities through unknown intermediates.
Renal and skeletal developmental involvement -> Skeletal-dysplasia-like abnormalities INDIRECT UNKNOWN INTERMEDIATES Skeletal dysplasia-like abnormalities are part of the severe neonatal branch.
Renal and skeletal developmental involvement -> Multicystic kidney dysplasia INDIRECT UNKNOWN INTERMEDIATES Multicystic kidneys expand the renal phenotype of severe ALG12-CDG.
Show evidence (2 references)
PMID:38717015 SUPPORT Human Clinical
"We report on a case expanding the phenotype of ALG12-CDG to include bilateral, multicystic kidneys in a neonatal demise identified with homozygous pathogenic variants in the ALG12 gene at c.1001del (p.N334Tfs*15) through clinical trio exome sequencing."
The report explicitly presents multicystic kidneys as an expanded severe prenatal phenotype rather than a universal ALG12-CDG manifestation.
PMID:38717015 SUPPORT Human Clinical
"In addition, skeletal abnormalities resembling a skeletal dysplasia including shortened long bones and talipes equinovarus have been seen in more severe neonatal presentation of this disorder."
The same report supports skeletal-dysplasia-like abnormalities as a limited severe neonatal extension of the phenotype.
Exceptional Adult Cardioskeletal Association Model
exceptional_adult_cardioskeletal_model EMERGING
Evidence balance 1 support
Ventricular septal defect and severe scoliosis were reported together in a single unusually mild adult. Coexisting ALG6 and KMT2D variants confound attribution, so this group records a bounded clinical association rather than a demonstrated causal consequence of ALG12 deficiency.
Pathograph links
Multisystem glycoprotein dysfunction -> Adult cardioskeletal structural involvement UNKNOWN Ventricular septal defect and severe scoliosis co-occurred in one exceptional adult, but their relationship to ALG12 dysfunction is unknown and confounded by coexisting variants.
Adult cardioskeletal structural involvement -> Ventricular septal defect UNKNOWN Ventricular septal defect was reported in one exceptional adult, but attribution to ALG12 deficiency is unknown and confounded by coexisting ALG6 and KMT2D variants.
Adult cardioskeletal structural involvement -> Scoliosis UNKNOWN Severe scoliosis was reported in one exceptional adult, but attribution to ALG12 deficiency is unknown and confounded by coexisting ALG6 and KMT2D variants.
Show evidence (1 reference)
PMID:32530140 SUPPORT Human Clinical
"We here present an intriguing patient with an exceptional phenotype: 25-year-old women with a ventricular septal defect and severe idiopathic scoliosis but no facial dysmorphism, who dances as a professional, and has a University degree."
The single-patient co-occurrence only partially supports this branch because the report discusses possible contributions from other variants.
⚙

Pathophysiology

9
ALG12 mannosyltransferase deficiency
Pathogenic ALG12 variants impair the alpha-mannosyltransferase step needed for dolichol-linked oligosaccharide biosynthesis and N-glycan precursor formation.
Canonical ALG12-CDG Glycoprotein Hypoglycosylation Model
ALG12 hgnc:19358 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves ALG12 (hgnc:19358). hgnc:19358 is a gene from the HUGO Gene Nomenclature Committee.
dolichol-linked oligosaccharide biosynthetic process GO:0006488 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased dolichol-linked oligosaccharide biosynthetic process (GO:0006488). GO:0006488 is a biological process from the Gene Ontology. ↓ DECREASED
mannosyltransferase activity GO:0000030 Gene Ontology (GO) Relation: this pathophysiological event involves this molecular function This pathophysiological event involves decreased mannosyltransferase activity (GO:0000030). GO:0000030 is a molecular function from the Gene Ontology. ↓ DECREASED
endoplasmic reticulum GO:0005783 Gene Ontology (GO) Relation: this pathophysiological event involves this cellular component This pathophysiological event involves endoplasmic reticulum (GO:0005783). GO:0005783 is a cellular component from the Gene Ontology.
Downstream
N-glycan precursor formation defect Loss of ALG12 alpha1,6-mannosyltransferase activity blocks addition of the eighth mannose to the dolichol-linked GlcNAc2Man7 intermediate, impairing completion of the N-glycan precursor used for transfer to proteins. Canonical ALG12-CDG Glycoprotein Hypoglycosylation Model
Show evidence (3 references)
PMID:34467644 SUPPORT Human Clinical
"Congenital disorder of glycosylation type Ig (ALG12-CDG) is a rare inherited metabolic disease caused by a defect in alpha-mannosyltransferase 8, encoded by the ALG12 gene (22q13.33)."
This directly identifies the disease-causing ALG12 enzyme defect.
CGGV:assertion_21631e85-8133-4703-a77c-c046effb6e56-2023-02-15T200000.000Z SUPPORT Other
"The mechanism of pathogenicity is known to be loss-of-function."
ClinGen supports loss of ALG12 function as the curated mechanism.
PMID:12217961 SUPPORT In Vitro
"In the patient's fibroblasts, the biosynthetic intermediate GlcNAc(2)Man(7) oligosaccharide was detected both on the lipid carrier dolichyl pyrophosphate and on newly synthesized glycoproteins, thus pointing to a defect in the dolichyl pyrophosphate-GlcNAc(2)Man(7)-dependent ALG12 alpha1,6..."
The original ALG12-CDG report directly localizes the ALG12 defect to dolichyl-pyrophosphate-linked oligosaccharide biosynthesis.
N-glycan precursor formation defect
Impaired N-glycan precursor formation leads to hypoglycosylation of transferrin and other plasma proteins, consistent with a type I CDG biochemical pattern.
Canonical ALG12-CDG Glycoprotein Hypoglycosylation Model
protein N-linked glycosylation GO:0006487 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased protein N-linked glycosylation (GO:0006487). GO:0006487 is a biological process from the Gene Ontology. ↓ DECREASED
Downstream
Abnormal serum and IgG N-glycosylation The precursor-assembly defect alters N-glycosylation-site occupancy and downstream glycan processing, producing abnormal total-serum and IgG N-glycan profiles; the intervening transfer and processing steps make this an indirect biochemical link. Canonical ALG12-CDG Glycoprotein Hypoglycosylation Model
Multisystem glycoprotein dysfunction Reduced N-glycosylation-site occupancy and abnormal glycan processing disrupt the folding, trafficking, and function of many glycoproteins, producing systemic dysfunction through incompletely resolved protein- and tissue-specific intermediates. Canonical ALG12-CDG Glycoprotein Hypoglycosylation Model
Show evidence (2 references)
PMID:34467644 SUPPORT Human Clinical
"Due to a newborn Slovak patient's clinical and biochemical abnormalities, the isoelectric focusing of transferrin was performed with observed significant hypoglycosylation typical of CDG I."
The transferrin result directly supports a type I CDG hypoglycosylation pattern.
PMID:31529350 SUPPORT Human Clinical
"Intact serum transferrin showed, as expected for a CDG type I defect, underoccupancy of N-glycosylation sites."
This supports protein N-glycosylation underoccupancy as a downstream biochemical consequence.
Multisystem glycoprotein dysfunction
Defective N-glycosylation disrupts many glycoproteins and is associated with neurodevelopmental, growth, immune, coagulation, dysmorphic, and genitourinary manifestations. Rare severe prenatal renal-skeletal and exceptional adult cardioskeletal observations are modeled as separately bounded branches rather than core consequences.
Canonical ALG12-CDG Glycoprotein Hypoglycosylation Model Exceptional Adult Cardioskeletal Association Model Severe Prenatal Renal-Skeletal Extension Model
protein N-linked glycosylation GO:0006487 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves abnormal protein N-linked glycosylation (GO:0006487). GO:0006487 is a biological process from the Gene Ontology. ⚠ ABNORMAL
Downstream
Neurodevelopmental and brain involvement Multisystem glycoprotein dysfunction is associated with neurologic and brain manifestations, but the affected glycoproteins and intervening developmental pathways are unresolved. Canonical ALG12-CDG Glycoprotein Hypoglycosylation Model
Growth and feeding impairment Multisystem ALG12-CDG is associated with impaired growth and feeding; the glycoprotein and tissue-specific intermediates are unresolved. Canonical ALG12-CDG Glycoprotein Hypoglycosylation Model
Dysmorphic and genitourinary developmental involvement Multisystem ALG12-CDG is associated with craniofacial dysmorphism and male genital hypoplasia through unresolved developmental intermediates. Canonical ALG12-CDG Glycoprotein Hypoglycosylation Model
Renal and skeletal developmental involvement Rare severe prenatal or neonatal reports associate ALG12-CDG with renal and skeletal developmental abnormalities through unknown intermediates. Severe Prenatal Renal-Skeletal Extension Model
Adult cardioskeletal structural involvement Ventricular septal defect and severe scoliosis co-occurred in one exceptional adult, but their relationship to ALG12 dysfunction is unknown and confounded by coexisting variants. Exceptional Adult Cardioskeletal Association Model
Show evidence (2 references)
PMID:38717015 SUPPORT Human Clinical
"Currently reported features of ALG12-CDG include: developmental delay, hypotonia, failure to thrive and/or short stature, brain anomalies, recurrent infections, hypogammaglobulinemia, coagulation abnormalities, and genitourinary abnormalities."
The report summarizes the multisystem clinical spectrum downstream of ALG12-associated glycoprotein dysfunction.
PMID:31481313 SUPPORT Human Clinical
"ALG12-congenital disorder of glycosylation (ALG12-CDG) is a rare disorder caused by a deficiency of dolichol-P-mannose:Man7GlcNAc2-PP-dolichyl-α-6-mannosyltransferase which presents with intellectual disability, hypotonia, dysmorphic features, low IgG levels with recurrent infections, male..."
The case series links ALG12 deficiency to a multisystem phenotype without resolving the glycoprotein or tissue-specific intermediates.
Abnormal serum and IgG N-glycosylation
Abnormal total-serum and IgG N-glycan profiles co-occur with low immunoglobulins, recurrent infections, and hypoglycosylated coagulation proteins. The evidence does not establish a specific responsible cell type or a direct causal path to the immune findings.
Canonical ALG12-CDG Glycoprotein Hypoglycosylation Model
protein N-linked glycosylation GO:0006487 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves abnormal protein N-linked glycosylation (GO:0006487). GO:0006487 is a biological process from the Gene Ontology. ⚠ ABNORMAL
Downstream
Decreased circulating immunoglobulin concentration Abnormal IgG N-glycosylation and low serum immunoglobulins co-occur in ALG12-CDG, but the evidence does not establish that the glycan-profile abnormality directly causes the decreased concentration. Canonical ALG12-CDG Glycoprotein Hypoglycosylation Model
Recurrent infections Recurrent infections co-occur with low immunoglobulins and abnormal IgG glycosylation, but the evidence does not establish a causal path from the measured glycan abnormality to infection susceptibility. Canonical ALG12-CDG Glycoprotein Hypoglycosylation Model
Abnormality of coagulation Hypoglycosylation and deficiency of factor XI provide a known protein-level intermediate linking systemic glycosylation abnormalities to an abnormal coagulation phenotype. Canonical ALG12-CDG Glycoprotein Hypoglycosylation Model
Show evidence (2 references)
PMID:31529350 SUPPORT Human Clinical
"ALG12-CDG is a severe multisystem disease associated with low to deficient serum immunoglobulins and recurrent infections."
The glycophenotype report links ALG12-CDG to low serum immunoglobulins and recurrent infections.
PMID:31529350 SUPPORT Human Clinical
"As a whole, ALG12-CDG behaves as a dual CDG (CDG-I and II defects) and it is associated with distinct, abnormal glycosylation of total serum and IgG N-glycans."
This supports abnormal IgG N-glycosylation as a disease-associated biochemical mechanism.
Neurodevelopmental and brain involvement
ALG12-CDG neurodevelopmental involvement includes developmental delay, intellectual disability, hypotonia, and reported brain anomalies.
Canonical ALG12-CDG Glycoprotein Hypoglycosylation Model
nervous system development GO:0007399 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves abnormal nervous system development (GO:0007399). GO:0007399 is a biological process from the Gene Ontology. ⚠ ABNORMAL
brain UBERON:0000955 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in brain (UBERON:0000955). UBERON:0000955 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Global developmental delay Developmental delay is part of the reported ALG12-CDG neurologic spectrum. Canonical ALG12-CDG Glycoprotein Hypoglycosylation Model
Intellectual disability Intellectual disability is part of the reported ALG12-CDG neurologic spectrum. Canonical ALG12-CDG Glycoprotein Hypoglycosylation Model
Hypotonia Hypotonia is part of the reported ALG12-CDG neurologic spectrum. Canonical ALG12-CDG Glycoprotein Hypoglycosylation Model
Show evidence (2 references)
PMID:38717015 SUPPORT Human Clinical
"Currently reported features of ALG12-CDG include: developmental delay, hypotonia, failure to thrive and/or short stature, brain anomalies, recurrent infections, hypogammaglobulinemia, coagulation abnormalities, and genitourinary abnormalities."
The prenatal phenotype report summarizes the neurologic and brain feature set reported in ALG12-CDG.
PMID:31481313 SUPPORT Human Clinical
"ALG12-congenital disorder of glycosylation (ALG12-CDG) is a rare disorder caused by a deficiency of dolichol-P-mannose:Man7GlcNAc2-PP-dolichyl-α-6-mannosyltransferase which presents with intellectual disability, hypotonia, dysmorphic features, low IgG levels with recurrent infections, male..."
The case-series abstract directly supports intellectual disability and hypotonia as neurologic manifestations.
Growth and feeding impairment
ALG12-CDG can impair somatic growth and feeding, presenting as failure to thrive, growth retardation, anorexia, or short stature.
Canonical ALG12-CDG Glycoprotein Hypoglycosylation Model
Downstream
Failure to thrive Failure to thrive is a reported growth manifestation of ALG12-CDG. Canonical ALG12-CDG Glycoprotein Hypoglycosylation Model
Short stature Short stature is a reported growth manifestation of ALG12-CDG. Canonical ALG12-CDG Glycoprotein Hypoglycosylation Model
Show evidence (2 references)
PMID:12217961 SUPPORT Human Clinical
"The severe disease was identified in a child presenting with psychomotor retardation, hypotonia, growth retardation, dysmorphic features and anorexia."
The original report describes growth retardation and anorexia in an ALG12-CDG child.
PMID:38717015 SUPPORT Human Clinical
"Currently reported features of ALG12-CDG include: developmental delay, hypotonia, failure to thrive and/or short stature, brain anomalies, recurrent infections, hypogammaglobulinemia, coagulation abnormalities, and genitourinary abnormalities."
The prenatal phenotype report summarizes failure to thrive and/or short stature in the broader ALG12-CDG phenotype.
Dysmorphic and genitourinary developmental involvement
ALG12-CDG can involve craniofacial dysmorphism and male genitourinary developmental abnormalities.
Canonical ALG12-CDG Glycoprotein Hypoglycosylation Model
Downstream
Facial dysmorphism Dysmorphic features include craniofacial involvement. Canonical ALG12-CDG Glycoprotein Hypoglycosylation Model
Hypoplastic male external genitalia Male genital hypoplasia is a genitourinary developmental manifestation. Canonical ALG12-CDG Glycoprotein Hypoglycosylation Model
Show evidence (2 references)
PMID:31481313 SUPPORT Human Clinical
"ALG12-congenital disorder of glycosylation (ALG12-CDG) is a rare disorder caused by a deficiency of dolichol-P-mannose:Man7GlcNAc2-PP-dolichyl-α-6-mannosyltransferase which presents with intellectual disability, hypotonia, dysmorphic features, low IgG levels with recurrent infections, male..."
The case-series abstract lists dysmorphic features and male genital hypoplasia in ALG12-CDG.
CGGV:assertion_21631e85-8133-4703-a77c-c046effb6e56-2023-02-15T200000.000Z SUPPORT Other
"Common phenotypes include intellectual disability, hypotonia, dysmorphic features, coagulation abnormalities and genitourinary abnormalities."
ClinGen independently lists dysmorphic and genitourinary abnormalities as common ALG12-CDG phenotypes.
Renal and skeletal developmental involvement
Severe ALG12-CDG can involve prenatal renal malformation and skeletal-dysplasia-like abnormalities.
Severe Prenatal Renal-Skeletal Extension Model
kidney development GO:0001822 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves abnormal kidney development (GO:0001822). GO:0001822 is a biological process from the Gene Ontology. ⚠ ABNORMAL skeletal system development GO:0001501 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves abnormal skeletal system development (GO:0001501). GO:0001501 is a biological process from the Gene Ontology. ⚠ ABNORMAL
kidney UBERON:0002113 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in kidney (UBERON:0002113). UBERON:0002113 is an anatomical location from the Uberon multi-species anatomy ontology. skeletal system UBERON:0001434 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in skeletal system (UBERON:0001434). UBERON:0001434 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Skeletal-dysplasia-like abnormalities Skeletal dysplasia-like abnormalities are part of the severe neonatal branch. Severe Prenatal Renal-Skeletal Extension Model
Multicystic kidney dysplasia Multicystic kidneys expand the renal phenotype of severe ALG12-CDG. Severe Prenatal Renal-Skeletal Extension Model
Show evidence (2 references)
PMID:38717015 SUPPORT Human Clinical
"In addition, skeletal abnormalities resembling a skeletal dysplasia including shortened long bones and talipes equinovarus have been seen in more severe neonatal presentation of this disorder."
The prenatal report supports skeletal-dysplasia-like abnormalities in severe neonatal ALG12-CDG.
PMID:38717015 SUPPORT Human Clinical
"We report on a case expanding the phenotype of ALG12-CDG to include bilateral, multicystic kidneys in a neonatal demise identified with homozygous pathogenic variants in the ALG12 gene at c.1001del (p.N334Tfs*15) through clinical trio exome sequencing."
The case report directly supports multicystic renal malformation in a severe prenatal ALG12-CDG presentation.
Adult cardioskeletal structural involvement
A single exceptional adult had ventricular septal defect and severe scoliosis. Coexisting ALG6 and KMT2D variants confound attribution, so this node records a bounded clinical association rather than an established consequence of ALG12 deficiency.
Exceptional Adult Cardioskeletal Association Model
heart UBERON:0000948 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in heart (UBERON:0000948). UBERON:0000948 is an anatomical location from the Uberon multi-species anatomy ontology. skeletal system UBERON:0001434 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in skeletal system (UBERON:0001434). UBERON:0001434 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Ventricular septal defect Ventricular septal defect was reported in one exceptional adult, but attribution to ALG12 deficiency is unknown and confounded by coexisting ALG6 and KMT2D variants. Exceptional Adult Cardioskeletal Association Model
Scoliosis Severe scoliosis was reported in one exceptional adult, but attribution to ALG12 deficiency is unknown and confounded by coexisting ALG6 and KMT2D variants. Exceptional Adult Cardioskeletal Association Model
Show evidence (1 reference)
PMID:32530140 SUPPORT Human Clinical
"We here present an intriguing patient with an exceptional phenotype: 25-year-old women with a ventricular septal defect and severe idiopathic scoliosis but no facial dysmorphism, who dances as a professional, and has a University degree."
The report establishes co-occurrence in one adult but only partially supports ALG12 attribution because other variants may contribute.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for ALG12-congenital disorder of glycosylation Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
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Phenotypes

14
Blood 2
Decreased circulating immunoglobulin concentration HP:0004313 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Hypogammaglobulinemia, annotated with Decreased circulating immunoglobulin concentration (HP:0004313). HP:0004313 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:31529350 SUPPORT Human Clinical
"ALG12-CDG is a severe multisystem disease associated with low to deficient serum immunoglobulins and recurrent infections."
The glycophenotype report directly supports low serum immunoglobulins.
Abnormality of coagulation HP:0001928 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Coagulation abnormalities, annotated with Abnormality of coagulation (HP:0001928). HP:0001928 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:38717015 SUPPORT Human Clinical
"Currently reported features of ALG12-CDG include: developmental delay, hypotonia, failure to thrive and/or short stature, brain anomalies, recurrent infections, hypogammaglobulinemia, coagulation abnormalities, and genitourinary abnormalities."
The case-series abstract lists coagulation abnormalities.
PMID:32530140 SUPPORT Human Clinical
"Increased levels of hypoglycosylated forms of F XI (also with significant deficiency) and transferrin were also detected."
The adult case demonstrates hypoglycosylation and deficiency of a coagulation factor.
Cardiovascular 1
Ventricular septal defect HP:0001629 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Ventricular septal defect (HP:0001629). HP:0001629 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:32530140 SUPPORT Human Clinical
"We here present an intriguing patient with an exceptional phenotype: 25-year-old women with a ventricular septal defect and severe idiopathic scoliosis but no facial dysmorphism, who dances as a professional, and has a University degree."
The report establishes the single-patient co-occurrence but not that the ventricular septal defect was caused by ALG12 deficiency.
PMID:32530140 SUPPORT Human Clinical
"In this context, we wonder what the contribution, if any, may be of the coexisting KMT2D variants and of the ALG6 variant."
The authors explicitly identify other-gene variants as possible modifiers of the exceptional adult phenotype.
Head and Neck 1
Facial dysmorphism Abnormal facial shape HP:0001999 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Facial dysmorphism, annotated with Abnormal facial shape (HP:0001999). HP:0001999 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:31481313 SUPPORT Human Clinical
"ALG12-congenital disorder of glycosylation (ALG12-CDG) is a rare disorder caused by a deficiency of dolichol-P-mannose:Man7GlcNAc2-PP-dolichyl-α-6-mannosyltransferase which presents with intellectual disability, hypotonia, dysmorphic features, low IgG levels with recurrent infections, male..."
The case-series abstract explicitly lists dysmorphic features in ALG12-CDG.
CGGV:assertion_21631e85-8133-4703-a77c-c046effb6e56-2023-02-15T200000.000Z SUPPORT Other
"Common phenotypes include intellectual disability, hypotonia, dysmorphic features, coagulation abnormalities and genitourinary abnormalities."
ClinGen independently lists dysmorphic features as common in ALG12-CDG.
Immune 1
Recurrent infections HP:0002719 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Recurrent infections (HP:0002719). HP:0002719 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:38717015 SUPPORT Human Clinical
"Currently reported features of ALG12-CDG include: developmental delay, hypotonia, failure to thrive and/or short stature, brain anomalies, recurrent infections, hypogammaglobulinemia, coagulation abnormalities, and genitourinary abnormalities."
The report lists recurrent infections among the currently reported ALG12-CDG features without restricting them to a specific organ system.
Musculoskeletal 3
Hypotonia HP:0001252 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Hypotonia (HP:0001252). HP:0001252 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:38717015 SUPPORT Human Clinical
"Currently reported features of ALG12-CDG include: developmental delay, hypotonia, failure to thrive and/or short stature, brain anomalies, recurrent infections, hypogammaglobulinemia, coagulation abnormalities, and genitourinary abnormalities."
The report lists hypotonia as a currently reported feature.
Skeletal-dysplasia-like abnormalities Abnormality of the skeletal system HP:0000924 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Skeletal-dysplasia-like abnormalities, annotated with Abnormality of the skeletal system (HP:0000924). HP:0000924 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:38717015 SUPPORT Human Clinical
"In addition, skeletal abnormalities resembling a skeletal dysplasia including shortened long bones and talipes equinovarus have been seen in more severe neonatal presentation of this disorder."
The prenatal phenotype report supports skeletal abnormalities resembling a dysplasia in severe neonatal ALG12-CDG without establishing a specific skeletal dysplasia diagnosis.
Scoliosis HP:0002650 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Scoliosis (HP:0002650). HP:0002650 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:32530140 SUPPORT Human Clinical
"We here present an intriguing patient with an exceptional phenotype: 25-year-old women with a ventricular septal defect and severe idiopathic scoliosis but no facial dysmorphism, who dances as a professional, and has a University degree."
The report establishes the single-patient co-occurrence but not that the scoliosis was caused by ALG12 deficiency.
PMID:32530140 SUPPORT Human Clinical
"In this context, we wonder what the contribution, if any, may be of the coexisting KMT2D variants and of the ALG6 variant."
The authors explicitly identify other-gene variants as possible modifiers of the exceptional adult phenotype.
Nervous System 2
Global developmental delay HP:0001263 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Global developmental delay (HP:0001263). HP:0001263 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:38717015 SUPPORT Human Clinical
"Currently reported features of ALG12-CDG include: developmental delay, hypotonia, failure to thrive and/or short stature, brain anomalies, recurrent infections, hypogammaglobulinemia, coagulation abnormalities, and genitourinary abnormalities."
The prenatal phenotype report summarizes developmental delay among reported ALG12-CDG features.
Intellectual disability HP:0001249 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Intellectual disability (HP:0001249). HP:0001249 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:31481313 SUPPORT Human Clinical
"ALG12-congenital disorder of glycosylation (ALG12-CDG) is a rare disorder caused by a deficiency of dolichol-P-mannose:Man7GlcNAc2-PP-dolichyl-α-6-mannosyltransferase which presents with intellectual disability, hypotonia, dysmorphic features, low IgG levels with recurrent infections, male..."
The case-series abstract directly lists intellectual disability among ALG12-CDG presenting features.
CGGV:assertion_21631e85-8133-4703-a77c-c046effb6e56-2023-02-15T200000.000Z SUPPORT Other
"Common phenotypes include intellectual disability, hypotonia, dysmorphic features, coagulation abnormalities and genitourinary abnormalities."
ClinGen names intellectual disability as a common phenotype for this gene-disease assertion.
Growth 2
Failure to thrive HP:0001508 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Failure to thrive (HP:0001508). HP:0001508 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:38717015 SUPPORT Human Clinical
"Currently reported features of ALG12-CDG include: developmental delay, hypotonia, failure to thrive and/or short stature, brain anomalies, recurrent infections, hypogammaglobulinemia, coagulation abnormalities, and genitourinary abnormalities."
The report lists failure to thrive among current features.
Short stature HP:0004322 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Short stature (HP:0004322). HP:0004322 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:38717015 SUPPORT Human Clinical
"Currently reported features of ALG12-CDG include: developmental delay, hypotonia, failure to thrive and/or short stature, brain anomalies, recurrent infections, hypogammaglobulinemia, coagulation abnormalities, and genitourinary abnormalities."
The report lists short stature as an alternate growth manifestation.
Other 2
Hypoplastic male external genitalia HP:0000050 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Male genital hypoplasia, annotated with Hypoplastic male external genitalia (HP:0000050). HP:0000050 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:31481313 SUPPORT Human Clinical
"ALG12-congenital disorder of glycosylation (ALG12-CDG) is a rare disorder caused by a deficiency of dolichol-P-mannose:Man7GlcNAc2-PP-dolichyl-α-6-mannosyltransferase which presents with intellectual disability, hypotonia, dysmorphic features, low IgG levels with recurrent infections, male..."
The Tahata case-series abstract directly lists male genital hypoplasia.
CGGV:assertion_21631e85-8133-4703-a77c-c046effb6e56-2023-02-15T200000.000Z SUPPORT Other
"Common phenotypes include intellectual disability, hypotonia, dysmorphic features, coagulation abnormalities and genitourinary abnormalities."
ClinGen supports genitourinary abnormalities as common in ALG12-CDG.
Multicystic kidney dysplasia HP:0000003 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Multicystic kidney dysplasia (HP:0000003). HP:0000003 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:38717015 SUPPORT Human Clinical
"We report on a case expanding the phenotype of ALG12-CDG to include bilateral, multicystic kidneys in a neonatal demise identified with homozygous pathogenic variants in the ALG12 gene at c.1001del (p.N334Tfs*15) through clinical trio exome sequencing."
This directly supports multicystic kidneys as a reported prenatal extension of the phenotype.
🧬

Genetic Associations

1
ALG12 (Biallelic loss-of-function variants)
Gene: ALG12 hgnc:19358 HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is ALG12 (hgnc:19358). hgnc:19358 is a gene from the HUGO Gene Nomenclature Committee. relationship_type: CAUSATIVE variant_origin: GERMLINE
Show evidence (3 references)
PMID:34467644 SUPPORT Human Clinical
"Genetic analysis of the coding regions of the ALG12 gene of the patient revealed a novel homozygous substitution mutation c.1439T>C p.(Leu480Pro) within Exon 10."
The case report documents a homozygous ALG12 variant in an affected patient.
PMID:38717015 SUPPORT Human Clinical
"We report on a case expanding the phenotype of ALG12-CDG to include bilateral, multicystic kidneys in a neonatal demise identified with homozygous pathogenic variants in the ALG12 gene at c.1001del (p.N334Tfs*15) through clinical trio exome sequencing."
The prenatal case report identifies a homozygous pathogenic ALG12 frameshift variant.
CGGV:assertion_21631e85-8133-4703-a77c-c046effb6e56-2023-02-15T200000.000Z SUPPORT Other
"In summary, there is definitive evidence to support the relationship between ALG12 and autosomal recessive ALG12 -congenital disorder of glycosylation."
ClinGen provides a deterministic structured assertion for the ALG12 gene-disease relationship.
💊

Medical Actions

1
Reported immunoglobulin infusions
Action: immunoglobulin infusion therapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is immunoglobulin infusion therapy, annotated with Immunoglobulin Therapy (NCIT:C62710). NCIT:C62710 is a clinical intervention from the NCI Thesaurus. Ontology label: Immunoglobulin Therapy NCIT:C62710
Agent: Therapeutic Immune Globulin NCIT:C2701 NCI Thesaurus (NCIT) Relation: this treatment uses this therapeutic agent This treatment uses Therapeutic Immune Globulin (NCIT:C2701). NCIT:C2701 is a therapeutic agent from the NCI Thesaurus.
Some ALG12-CDG patients with low circulating immunoglobulins have received immunoglobulin infusions. A 2024 review describes the reported response as apparently unsuccessful, so this records observed treatment use rather than an established effective ALG12-CDG therapy.
Target Phenotypes: Hypogammaglobulinemia HP:0004313 Human Phenotype Ontology (HP) Relation: this treatment targets this phenotype This treatment targets Hypogammaglobulinemia, annotated with Decreased circulating immunoglobulin concentration (HP:0004313). HP:0004313 is a phenotype from the Human Phenotype Ontology. Recurrent infections HP:0002719 Human Phenotype Ontology (HP) Relation: this treatment targets this phenotype This treatment targets Recurrent infections (HP:0002719). HP:0002719 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:38550576 SUPPORT Other
"some ALG12-CDG patients have been treated with Ig infusions with apparent no success"
The review documents reported Ig-infusion use and apparent lack of success; it does not establish treatment benefit.
🔬

Biochemical Markers

3
Type I transferrin hypoglycosylation pattern (Present)
Pathograph Readouts
Readout Of N-glycan precursor formation defect Present Absent Diagnostic
A type I transferrin hypoglycosylation pattern reports impaired N-glycosylation-site occupancy downstream of the ALG12 precursor defect.
Show evidence (1 reference)
PMID:31529350 SUPPORT Human Clinical
"Intact serum transferrin showed, as expected for a CDG type I defect, underoccupancy of N-glycosylation sites."
The patient-serum result directly supports transferrin underoccupancy as a readout of the precursor-assembly defect.
Show evidence (1 reference)
PMID:34467644 SUPPORT Human Clinical
"Due to a newborn Slovak patient's clinical and biochemical abnormalities, the isoelectric focusing of transferrin was performed with observed significant hypoglycosylation typical of CDG I."
This directly supports transferrin isoelectric focusing as a biochemical marker of type I CDG in ALG12-CDG.
Aberrant serum oligomannose N-glycan profile (Present)
Pathograph Readouts
Readout Of ALG12 mannosyltransferase deficiency Present Absent Diagnostic
Accumulation of GlcNAc2Man5-7 with reduced GlcNAc2Man8-9 reports impaired ALG12 enzymatic activity.
Show evidence (1 reference)
PMID:34467644 SUPPORT Human Clinical
"Furthermore, analysis of neutral serum N-glycans by mass spectrometry revealed the accumulation of GlcNAc2Man5-7 and decreased levels of GlcNAc2Man8-9, which indicated impaired ALG12 enzymatic activity."
The single-patient serum profile directly supports this readout of impaired ALG12 activity.
Show evidence (1 reference)
PMID:34467644 SUPPORT Human Clinical
"Furthermore, analysis of neutral serum N-glycans by mass spectrometry revealed the accumulation of GlcNAc2Man5-7 and decreased levels of GlcNAc2Man8-9, which indicated impaired ALG12 enzymatic activity."
Serum N-glycan profiling directly supports an ALG12-associated oligomannose signature.
Hypoglycosylated antithrombin and factor XI (Present)
Pathograph Readouts
Readout Of Abnormal serum and IgG N-glycosylation Present Absent Diagnostic
Hypoglycosylated coagulation proteins report systemic plasma-protein hypoglycosylation caused by the ALG12-CDG glycosylation defect.
Show evidence (1 reference)
PMID:32530140 SUPPORT Human Clinical
"Increased levels of hypoglycosylated forms of F XI (also with significant deficiency) and transferrin were also detected."
Detection of hypoglycosylated factor XI directly supports the plasma-protein hypoglycosylation readout.
Show evidence (2 references)
PMID:32530140 SUPPORT Human Clinical
"Congenital disorder of glycosylation diagnosis started through the identification of antithrombin deficiency without SERPINC1 defect and the detection of hypoglycosylated forms."
The adult case shows a coagulation-protein hypoglycosylation clue to diagnosis.
PMID:32530140 SUPPORT Human Clinical
"Increased levels of hypoglycosylated forms of F XI (also with significant deficiency) and transferrin were also detected."
This directly supports hypoglycosylated and deficient factor XI in the reported patient.
🔬

Diagnosis

3
Transferrin isoelectric focusing screening
Transferrin isoelectric focusing can detect a type I protein N-glycosylation pattern, but that pattern is shared across multiple CDG subtypes and does not identify ALG12-CDG by itself.
clinical laboratory procedure NCIT:C25294 NCI Thesaurus (NCIT)
Results: A type I transferrin hypoglycosylation pattern supports a disorder of early protein N-glycosylation and should prompt molecular subtype evaluation; it is not specific for ALG12-CDG.
Show evidence (2 references)
PMID:34467644 SUPPORT Human Clinical
"Due to a newborn Slovak patient's clinical and biochemical abnormalities, the isoelectric focusing of transferrin was performed with observed significant hypoglycosylation typical of CDG I."
This patient result supports transferrin isoelectric focusing as a biochemical screen for a type I CDG pattern.
PMID:31529350 SUPPORT Human Clinical
"We analyzed serum native transferrin, as first line test for CDG"
This directly supports serum transferrin testing as a first-line CDG screen, without implying ALG12 specificity.
Serum N-glycan profiling
Mass-spectrometric serum N-glycan profiling identified an oligomannose pattern consistent with impaired ALG12 activity in one reported patient; its sensitivity and specificity as an ALG12-CDG diagnostic test are not established.
clinical laboratory procedure NCIT:C25294 NCI Thesaurus (NCIT)
Results: Accumulation of GlcNAc2Man5-7 with decreased GlcNAc2Man8-9 can provide supporting biochemical evidence for impaired ALG12 activity, but molecular confirmation is required.
Show evidence (1 reference)
PMID:34467644 SUPPORT Human Clinical
"Furthermore, analysis of neutral serum N-glycans by mass spectrometry revealed the accumulation of GlcNAc2Man5-7 and decreased levels of GlcNAc2Man8-9, which indicated impaired ALG12 enzymatic activity."
This single-patient result supports the reported ALG12-associated glycomic signature without establishing population-level diagnostic performance.
ALG12 molecular genetic testing
Molecular diagnosis is established by identifying biallelic pathogenic or likely pathogenic ALG12 variants; compound-heterozygous alleles should be shown or inferred to be in trans. Compatible glycosylation findings can support variant interpretation but are not themselves ALG12-specific.
molecular genetic testing NCIT:C19770 NCI Thesaurus (NCIT)
Results: Homozygous or in-trans compound-heterozygous pathogenic or likely pathogenic ALG12 variants establish the molecular diagnosis; biochemical findings provide supporting pathway evidence.
Show evidence (2 references)
PMID:34467644 SUPPORT Human Clinical
"This comprehensive genomic and glycomic approach led to the confirmation of the ALG12 pathogenic variant responsible for the clinical manifestation of the disorder in the patient described."
The case report directly supports combined genomic and glycomic confirmation of the diagnosis.
PMID:37644541 SUPPORT Other
"CDG diagnosis has been at a rapid pace since the introduction of whole-exome/whole-genome sequencing as a diagnostic tool."
This CDG-wide review supports genome-scale sequencing as a modern diagnostic approach for CDG; it is broader than ALG12-CDG alone.
📈

Progression

1
Variable severity
ALG12-CDG severity ranges from mild adult presentations to fatal multisystem infantile disease.
Show evidence (1 reference)
PMID:31481313 SUPPORT Human Clinical
"We report a unique family with three affected individuals, including two older brothers with only cognitive and coagulation defects and a younger brother who died from a severe multisystem disease at age 18 months. The two living brothers are the oldest and mildest cases of ALG12-CDG described thus far."
The within-family case series directly contrasts the mildest and oldest reported survivors with a sibling who died from severe multisystem disease at 18 months.
📊

Prevalence

1
Global published literature
Cases In Literature Ultra Rare
As of 2021, the cited report stated that 15 patients had been diagnosed globally. This is a time-bounded diagnosed-case count from the literature, not a population prevalence estimate.
Show evidence (1 reference)
PMID:34467644 SUPPORT Human Clinical
"To date, only 15 patients have been diagnosed with ALG12-CDG globally."
The 2021 case report provides a direct published patient-count estimate.
🔬

Clinical Trials

1
NCT04199000 RECRUITING
Recruiting CDG-wide observational natural-history study relevant to broadly eligible, confirmed CDG subtypes such as ALG12-CDG. It is not an interventional trial and does not test ALG12-specific treatment efficacy.
Show evidence (1 reference)
clinicaltrials:NCT04199000 SUPPORT Human Clinical
"The purpose of this research is to study the natural history of congenital disorders of glycosylation and its causes and treatments."
The study is CDG-wide and observational rather than an ALG12-specific efficacy trial, so the registry summary provides only partial support for ALG12-CDG relevance.
{ }

Source YAML

click to show 
name: ALG12-congenital disorder of glycosylation
creation_date: "2026-05-10T18:41:07Z"
description: >-
  ALG12-congenital disorder of glycosylation is a rare autosomal recessive
  disorder of protein N-linked glycosylation caused by biallelic ALG12
  variants. Loss of ALG12 mannosyltransferase activity disrupts
  N-glycan-precursor formation, produces a type I congenital disorder of
  glycosylation biochemical pattern, and causes variable neurodevelopmental,
  immune, coagulation, growth, skeletal, cardiac, and prenatal manifestations.
category: Mendelian
disease_term:
  preferred_term: ALG12-congenital disorder of glycosylation
  term:
    id: MONDO:0011783
    label: ALG12-congenital disorder of glycosylation
parents:
- congenital disorder of glycosylation type I
- disorder of protein N-glycosylation
synonyms:
- ALG12-CDG
- CDG-Ig
- CDG1G
- congenital disorder of glycosylation type Ig
- mannosyltransferase 8 deficiency
inheritance:
- name: Autosomal recessive inheritance
  inheritance_term:
    preferred_term: Autosomal recessive inheritance
    term:
      id: HP:0000007
      label: Autosomal recessive inheritance
  description: >-
    ALG12-CDG is an autosomal recessive condition caused by biallelic
    pathogenic ALG12 variants.
  evidence:
  - reference: PMID:38717015
    reference_title: Expanded prenatal phenotype of ALG12-associated congenital disorder of glycosylation including bilateral multicystic kidneys.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      ALG12-CDG specifically is caused by biallelic pathogenic variants in
      ALG12.
    explanation: >-
      The 2024 prenatal case report directly states biallelic ALG12 causation.
  - reference: CGGV:assertion_21631e85-8133-4703-a77c-c046effb6e56-2023-02-15T200000.000Z
    reference_title: "ALG12 / ALG12-congenital disorder of glycosylation (Definitive)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "ALG12 | HGNC:19358 | ALG12-congenital disorder of glycosylation | MONDO:0011783 | AR | Definitive"
    explanation: >-
      ClinGen classifies the ALG12-ALG12-CDG relationship as definitive with
      autosomal recessive inheritance.
prevalence:
- population: Global published literature
  measure_type: CASES_IN_LITERATURE
  prevalence_class: ULTRA_RARE
  notes: >-
    As of 2021, the cited report stated that 15 patients had been diagnosed
    globally. This is a time-bounded diagnosed-case count from the literature,
    not a population prevalence estimate.
  evidence:
  - reference: PMID:34467644
    reference_title: A novel homozygous mutation in the human ALG12 gene results in an aberrant profile of oligomannose N-glycans in patient's serum.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      To date, only 15 patients have been diagnosed with ALG12-CDG globally.
    explanation: >-
      The 2021 case report provides a direct published patient-count estimate.
progression:
- phase: Variable severity
  notes: >-
    ALG12-CDG severity ranges from mild adult presentations to fatal
    multisystem infantile disease.
  evidence:
  - reference: PMID:31481313
    reference_title: "Complex phenotypes in ALG12-congenital disorder of glycosylation (ALG12-CDG): Case series and review of the literature."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We report a unique family with three affected individuals, including two
      older brothers with only cognitive and coagulation defects and a younger
      brother who died from a severe multisystem disease at age 18 months. The
      two living brothers are the oldest and mildest cases of ALG12-CDG
      described thus far.
    explanation: >-
      The within-family case series directly contrasts the mildest and oldest
      reported survivors with a sibling who died from severe multisystem disease
      at 18 months.
mechanistic_hypotheses:
- hypothesis_group_id: canonical_alg12_cdg_model
  hypothesis_label: Canonical ALG12-CDG Glycoprotein Hypoglycosylation Model
  status: CANONICAL
  description: >-
    Biallelic loss of ALG12 function reduces the ER alpha1,6-mannosyltransferase
    step in lipid-linked oligosaccharide assembly. The resulting precursor
    defect causes underoccupancy and abnormal N-glycosylation of multiple
    proteins and a multisystem CDG phenotype. The biochemical sequence is
    canonical, while the tissue-specific intermediates connecting systemic
    glycoprotein dysfunction to individual clinical findings remain unresolved.
  evidence:
  - reference: PMID:12217961
    reference_title: ALG12 mannosyltransferase defect in congenital disorder of glycosylation type lg.
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      In the patient's fibroblasts, the biosynthetic intermediate
      GlcNAc(2)Man(7) oligosaccharide was detected both on the lipid carrier
      dolichyl pyrophosphate and on newly synthesized glycoproteins, thus
      pointing to a defect in the dolichyl pyrophosphate-GlcNAc(2)Man(7)-dependent
      ALG12 alpha1,6 mannosyltransferase.
    explanation: >-
      Patient-fibroblast measurements directly support the ALG12
      precursor-assembly defect at the center of the canonical model.
- hypothesis_group_id: severe_prenatal_renal_skeletal_model
  hypothesis_label: Severe Prenatal Renal-Skeletal Extension Model
  status: EMERGING
  description: >-
    A rare severe prenatal or neonatal branch may extend ALG12-CDG to
    multicystic renal malformation and skeletal-dysplasia-like abnormalities.
    This branch is kept separate from the canonical clinical spectrum because
    it is supported by limited severe-case evidence and its organ-specific
    intermediates are unknown.
  evidence:
  - reference: PMID:38717015
    reference_title: Expanded prenatal phenotype of ALG12-associated congenital disorder of glycosylation including bilateral multicystic kidneys.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We report on a case expanding the phenotype of ALG12-CDG to include
      bilateral, multicystic kidneys in a neonatal demise identified with
      homozygous pathogenic variants in the ALG12 gene at c.1001del
      (p.N334Tfs*15) through clinical trio exome sequencing.
    explanation: >-
      The report explicitly presents multicystic kidneys as an expanded severe
      prenatal phenotype rather than a universal ALG12-CDG manifestation.
  - reference: PMID:38717015
    reference_title: Expanded prenatal phenotype of ALG12-associated congenital disorder of glycosylation including bilateral multicystic kidneys.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      In addition, skeletal abnormalities resembling a skeletal dysplasia
      including shortened long bones and talipes equinovarus have been seen in
      more severe neonatal presentation of this disorder.
    explanation: >-
      The same report supports skeletal-dysplasia-like abnormalities as a
      limited severe neonatal extension of the phenotype.
- hypothesis_group_id: exceptional_adult_cardioskeletal_model
  hypothesis_label: Exceptional Adult Cardioskeletal Association Model
  status: EMERGING
  description: >-
    Ventricular septal defect and severe scoliosis were reported together in a
    single unusually mild adult. Coexisting ALG6 and KMT2D variants confound
    attribution, so this group records a bounded clinical association rather
    than a demonstrated causal consequence of ALG12 deficiency.
  evidence:
  - reference: PMID:32530140
    reference_title: "ALG12-CDG: An unusual patient without intellectual disability and facial dysmorphism, and with a novel variant."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We here present an intriguing patient with an exceptional phenotype:
      25-year-old women with a ventricular septal defect and severe idiopathic
      scoliosis but no facial dysmorphism, who dances as a professional, and
      has a University degree.
    explanation: >-
      The single-patient co-occurrence only partially supports this branch
      because the report discusses possible contributions from other variants.
pathophysiology:
- name: ALG12 mannosyltransferase deficiency
  conforms_to: "congenital_disorder_of_glycosylation#ER Lipid-Linked Oligosaccharide Assembly Defect"
  description: >-
    Pathogenic ALG12 variants impair the alpha-mannosyltransferase step needed
    for dolichol-linked oligosaccharide biosynthesis and N-glycan precursor
    formation.
  genes:
  - preferred_term: ALG12
    term:
      id: hgnc:19358
      label: ALG12
  biological_processes:
  - preferred_term: dolichol-linked oligosaccharide biosynthetic process
    modifier: DECREASED
    term:
      id: GO:0006488
      label: dolichol-linked oligosaccharide biosynthetic process
  molecular_functions:
  - preferred_term: mannosyltransferase activity
    modifier: DECREASED
    term:
      id: GO:0000030
      label: mannosyltransferase activity
  cellular_components:
  - preferred_term: endoplasmic reticulum
    term:
      id: GO:0005783
      label: endoplasmic reticulum
  evidence:
  - reference: PMID:34467644
    reference_title: A novel homozygous mutation in the human ALG12 gene results in an aberrant profile of oligomannose N-glycans in patient's serum.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Congenital disorder of glycosylation type Ig (ALG12-CDG) is a rare
      inherited metabolic disease caused by a defect in alpha-mannosyltransferase
      8, encoded by the ALG12 gene (22q13.33).
    explanation: >-
      This directly identifies the disease-causing ALG12 enzyme defect.
  - reference: CGGV:assertion_21631e85-8133-4703-a77c-c046effb6e56-2023-02-15T200000.000Z
    reference_title: "ALG12 / ALG12-congenital disorder of glycosylation (Definitive)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The mechanism of pathogenicity is known to be loss-of-function.
    explanation: >-
      ClinGen supports loss of ALG12 function as the curated mechanism.
  - reference: PMID:12217961
    reference_title: ALG12 mannosyltransferase defect in congenital disorder of glycosylation type lg.
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      In the patient's fibroblasts, the biosynthetic intermediate
      GlcNAc(2)Man(7) oligosaccharide was detected both on the lipid carrier
      dolichyl pyrophosphate and on newly synthesized glycoproteins, thus
      pointing to a defect in the dolichyl pyrophosphate-GlcNAc(2)Man(7)-dependent
      ALG12 alpha1,6 mannosyltransferase.
    explanation: >-
      The original ALG12-CDG report directly localizes the ALG12 defect to
      dolichyl-pyrophosphate-linked oligosaccharide biosynthesis.
  downstream:
  - target: N-glycan precursor formation defect
    description: >-
      Loss of ALG12 alpha1,6-mannosyltransferase activity blocks addition of the
      eighth mannose to the dolichol-linked GlcNAc2Man7 intermediate, impairing
      completion of the N-glycan precursor used for transfer to proteins.
    causal_link_type: DIRECT
    hypothesis_groups:
    - canonical_alg12_cdg_model
    evidence:
    - reference: PMID:12217961
      reference_title: ALG12 mannosyltransferase defect in congenital disorder of glycosylation type lg.
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: >-
        In the patient's fibroblasts, the biosynthetic intermediate
        GlcNAc(2)Man(7) oligosaccharide was detected both on the lipid carrier
        dolichyl pyrophosphate and on newly synthesized glycoproteins, thus
        pointing to a defect in the dolichyl pyrophosphate-GlcNAc(2)Man(7)-dependent
        ALG12 alpha1,6 mannosyltransferase.
      explanation: >-
        Patient-fibroblast accumulation of the ALG12 substrate directly links
        deficient ALG12 activity to the precursor-assembly defect.
- name: N-glycan precursor formation defect
  conforms_to: "congenital_disorder_of_glycosylation#Protein Hypoglycosylation"
  description: >-
    Impaired N-glycan precursor formation leads to hypoglycosylation of
    transferrin and other plasma proteins, consistent with a type I CDG
    biochemical pattern.
  biological_processes:
  - preferred_term: protein N-linked glycosylation
    modifier: DECREASED
    term:
      id: GO:0006487
      label: protein N-linked glycosylation
  chemical_entities:
  - preferred_term: N-glycan precursor
    modifier: ABNORMAL
    term:
      id: CHEBI:59520
      label: N-glycan
  evidence:
  - reference: PMID:34467644
    reference_title: A novel homozygous mutation in the human ALG12 gene results in an aberrant profile of oligomannose N-glycans in patient's serum.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Due to a newborn Slovak patient's clinical and biochemical abnormalities,
      the isoelectric focusing of transferrin was performed with observed
      significant hypoglycosylation typical of CDG I.
    explanation: >-
      The transferrin result directly supports a type I CDG hypoglycosylation
      pattern.
  - reference: PMID:31529350
    reference_title: "ALG12-CDG: novel glycophenotype insights endorse the molecular defect."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Intact serum transferrin showed, as expected for a CDG type I defect,
      underoccupancy of N-glycosylation sites.
    explanation: >-
      This supports protein N-glycosylation underoccupancy as a downstream
      biochemical consequence.
  downstream:
  - target: Abnormal serum and IgG N-glycosylation
    description: >-
      The precursor-assembly defect alters N-glycosylation-site occupancy and
      downstream glycan processing, producing abnormal total-serum and IgG
      N-glycan profiles; the intervening transfer and processing steps make
      this an indirect biochemical link.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Transfer of incomplete lipid-linked oligosaccharides, reduced protein N-glycosylation-site occupancy, and downstream glycan processing.
    hypothesis_groups:
    - canonical_alg12_cdg_model
    evidence:
    - reference: PMID:34467644
      reference_title: A novel homozygous mutation in the human ALG12 gene results in an aberrant profile of oligomannose N-glycans in patient's serum.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Furthermore, analysis of neutral serum N-glycans by mass spectrometry
        revealed the accumulation of GlcNAc2Man5-7 and decreased levels of
        GlcNAc2Man8-9, which indicated impaired ALG12 enzymatic activity.
      explanation: >-
        Serum N-glycan mass spectrometry directly links abnormal N-glycan
        species to impaired ALG12 activity.
    - reference: PMID:31529350
      reference_title: "ALG12-CDG: novel glycophenotype insights endorse the molecular defect."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        As a whole, ALG12-CDG behaves as a dual CDG (CDG-I and II defects) and
        it is associated with distinct, abnormal glycosylation of total serum
        and IgG N-glycans.
      explanation: >-
        This supports downstream abnormal glycosylation of total serum and IgG
        N-glycans.
  - target: Multisystem glycoprotein dysfunction
    description: >-
      Reduced N-glycosylation-site occupancy and abnormal glycan processing
      disrupt the folding, trafficking, and function of many glycoproteins,
      producing systemic dysfunction through incompletely resolved protein- and
      tissue-specific intermediates.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    hypothesis_groups:
    - canonical_alg12_cdg_model
    evidence:
    - reference: PMID:32530140
      reference_title: "ALG12-CDG: An unusual patient without intellectual disability and facial dysmorphism, and with a novel variant."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        The relevance of N‐glycosylation for the folding, intracellular
        trafficking, and function of many proteins, particularly during
        development, support multiple mostly severe clinical phenotypes usually
        comprising also neurological involvement.
      explanation: >-
        The clinical report supports broad glycoprotein dysfunction as the
        bridge to multisystem disease, while the individual intermediates remain
        unresolved.
- name: Multisystem glycoprotein dysfunction
  conforms_to: "congenital_disorder_of_glycosylation#Multisystem Glycoprotein Dysfunction"
  description: >-
    Defective N-glycosylation disrupts many glycoproteins and is associated
    with neurodevelopmental, growth, immune, coagulation, dysmorphic, and
    genitourinary manifestations. Rare severe prenatal renal-skeletal and
    exceptional adult cardioskeletal observations are modeled as separately
    bounded branches rather than core consequences.
  biological_processes:
  - preferred_term: protein N-linked glycosylation
    modifier: ABNORMAL
    term:
      id: GO:0006487
      label: protein N-linked glycosylation
  evidence:
  - reference: PMID:38717015
    reference_title: Expanded prenatal phenotype of ALG12-associated congenital disorder of glycosylation including bilateral multicystic kidneys.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Currently reported features of ALG12-CDG include: developmental delay,
      hypotonia, failure to thrive and/or short stature, brain anomalies,
      recurrent infections, hypogammaglobulinemia, coagulation abnormalities,
      and genitourinary abnormalities.
    explanation: >-
      The report summarizes the multisystem clinical spectrum downstream of
      ALG12-associated glycoprotein dysfunction.
  - reference: PMID:31481313
    reference_title: "Complex phenotypes in ALG12-congenital disorder of glycosylation (ALG12-CDG): Case series and review of the literature."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      ALG12-congenital disorder of glycosylation (ALG12-CDG) is a rare disorder
      caused by a deficiency of
      dolichol-P-mannose:Man7GlcNAc2-PP-dolichyl-α-6-mannosyltransferase which
      presents with intellectual disability, hypotonia, dysmorphic features, low
      IgG levels with recurrent infections, male genital hypoplasia, and
      coagulation abnormalities.
    explanation: >-
      The case series links ALG12 deficiency to a multisystem phenotype without
      resolving the glycoprotein or tissue-specific intermediates.
  downstream:
  - target: Neurodevelopmental and brain involvement
    description: >-
      Multisystem glycoprotein dysfunction is associated with neurologic and
      brain manifestations, but the affected glycoproteins and intervening
      developmental pathways are unresolved.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    hypothesis_groups:
    - canonical_alg12_cdg_model
    evidence:
    - reference: PMID:32530140
      reference_title: "ALG12-CDG: An unusual patient without intellectual disability and facial dysmorphism, and with a novel variant."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        The relevance of N‐glycosylation for the folding, intracellular
        trafficking, and function of many proteins, particularly during
        development, support multiple mostly severe clinical phenotypes usually
        comprising also neurological involvement.
      explanation: >-
        The report supports a general glycoprotein-folding and trafficking link
        to neurologic disease while leaving the specific intermediates unknown.
  - target: Growth and feeding impairment
    description: >-
      Multisystem ALG12-CDG is associated with impaired growth and feeding;
      the glycoprotein and tissue-specific intermediates are unresolved.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    hypothesis_groups:
    - canonical_alg12_cdg_model
    evidence:
    - reference: PMID:12217961
      reference_title: ALG12 mannosyltransferase defect in congenital disorder of glycosylation type lg.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        The severe disease was identified in a child presenting with psychomotor
        retardation, hypotonia, growth retardation, dysmorphic features and
        anorexia.
      explanation: >-
        The original ALG12-CDG report supports the clinical association with
        growth retardation and anorexia.
  - target: Dysmorphic and genitourinary developmental involvement
    description: >-
      Multisystem ALG12-CDG is associated with craniofacial dysmorphism and male
      genital hypoplasia through unresolved developmental intermediates.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    hypothesis_groups:
    - canonical_alg12_cdg_model
    evidence:
    - reference: PMID:31481313
      reference_title: "Complex phenotypes in ALG12-congenital disorder of glycosylation (ALG12-CDG): Case series and review of the literature."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        ALG12-congenital disorder of glycosylation (ALG12-CDG) is a rare
        disorder caused by a deficiency of
        dolichol-P-mannose:Man7GlcNAc2-PP-dolichyl-α-6-mannosyltransferase
        which presents with intellectual disability, hypotonia, dysmorphic
        features, low IgG levels with recurrent infections, male genital
        hypoplasia, and coagulation abnormalities.
      explanation: >-
        The case-series abstract supports the dysmorphic and genitourinary
        clinical branch without establishing its intervening mechanism.
  - target: Renal and skeletal developmental involvement
    description: >-
      Rare severe prenatal or neonatal reports associate ALG12-CDG with renal
      and skeletal developmental abnormalities through unknown intermediates.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    hypothesis_groups:
    - severe_prenatal_renal_skeletal_model
    evidence:
    - reference: PMID:38717015
      reference_title: Expanded prenatal phenotype of ALG12-associated congenital disorder of glycosylation including bilateral multicystic kidneys.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        In addition, skeletal abnormalities resembling a skeletal dysplasia
        including shortened long bones and talipes equinovarus have been seen in
        more severe neonatal presentation of this disorder.
      explanation: >-
        The report supports a severe neonatal skeletal extension, kept outside
        the canonical clinical branches because evidence remains limited.
    - reference: PMID:38717015
      reference_title: Expanded prenatal phenotype of ALG12-associated congenital disorder of glycosylation including bilateral multicystic kidneys.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        We report on a case expanding the phenotype of ALG12-CDG to include
        bilateral, multicystic kidneys in a neonatal demise identified with
        homozygous pathogenic variants in the ALG12 gene at c.1001del
        (p.N334Tfs*15) through clinical trio exome sequencing.
      explanation: >-
        The report directly supports the renal half of this bounded severe
        prenatal renal-skeletal branch.
  - target: Adult cardioskeletal structural involvement
    description: >-
      Ventricular septal defect and severe scoliosis co-occurred in one
      exceptional adult, but their relationship to ALG12 dysfunction is unknown
      and confounded by coexisting variants.
    causal_link_type: UNKNOWN
    hypothesis_groups:
    - exceptional_adult_cardioskeletal_model
    evidence:
    - reference: PMID:32530140
      reference_title: "ALG12-CDG: An unusual patient without intellectual disability and facial dysmorphism, and with a novel variant."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        We here present an intriguing patient with an exceptional phenotype:
        25-year-old women with a ventricular septal defect and severe idiopathic
        scoliosis but no facial dysmorphism, who dances as a professional, and
        has a University degree.
      explanation: >-
        This single-patient co-occurrence only partially supports the branch;
        possible contributions from other variants prevent causal attribution.
- name: Abnormal serum and IgG N-glycosylation
  description: >-
    Abnormal total-serum and IgG N-glycan profiles co-occur with low
    immunoglobulins, recurrent infections, and hypoglycosylated coagulation
    proteins. The evidence does not establish a specific responsible cell type
    or a direct causal path to the immune findings.
  biological_processes:
  - preferred_term: protein N-linked glycosylation
    modifier: ABNORMAL
    term:
      id: GO:0006487
      label: protein N-linked glycosylation
  evidence:
  - reference: PMID:31529350
    reference_title: "ALG12-CDG: novel glycophenotype insights endorse the molecular defect."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      ALG12-CDG is a severe multisystem disease associated with low to
      deficient serum immunoglobulins and recurrent infections.
    explanation: >-
      The glycophenotype report links ALG12-CDG to low serum immunoglobulins
      and recurrent infections.
  - reference: PMID:31529350
    reference_title: "ALG12-CDG: novel glycophenotype insights endorse the molecular defect."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      As a whole, ALG12-CDG behaves as a dual CDG (CDG-I and II defects) and it
      is associated with distinct, abnormal glycosylation of total serum and IgG
      N-glycans.
    explanation: >-
      This supports abnormal IgG N-glycosylation as a disease-associated
      biochemical mechanism.
  downstream:
  - target: Decreased circulating immunoglobulin concentration
    description: >-
      Abnormal IgG N-glycosylation and low serum immunoglobulins co-occur in
      ALG12-CDG, but the evidence does not establish that the glycan-profile
      abnormality directly causes the decreased concentration.
    causal_link_type: UNKNOWN
    hypothesis_groups:
    - canonical_alg12_cdg_model
    evidence:
    - reference: PMID:31529350
      reference_title: "ALG12-CDG: novel glycophenotype insights endorse the molecular defect."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        ALG12-CDG is a severe multisystem disease associated with low to
        deficient serum immunoglobulins and recurrent infections.
      explanation: >-
        The study supports co-occurrence of the glycosylation phenotype and low
        immunoglobulins, not a direct causal link between them.
  - target: Recurrent infections
    description: >-
      Recurrent infections co-occur with low immunoglobulins and abnormal IgG
      glycosylation, but the evidence does not establish a causal path from the
      measured glycan abnormality to infection susceptibility.
    causal_link_type: UNKNOWN
    hypothesis_groups:
    - canonical_alg12_cdg_model
    evidence:
    - reference: PMID:31529350
      reference_title: "ALG12-CDG: novel glycophenotype insights endorse the molecular defect."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        ALG12-CDG is a severe multisystem disease associated with low to
        deficient serum immunoglobulins and recurrent infections.
      explanation: >-
        The report supports the clinical association among abnormal glycosylation,
        low immunoglobulins, and recurrent infections without resolving causality.
  - target: Abnormality of coagulation
    description: >-
      Hypoglycosylation and deficiency of factor XI provide a known protein-level
      intermediate linking systemic glycosylation abnormalities to an abnormal
      coagulation phenotype.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Hypoglycosylation and deficiency of coagulation factor XI.
    hypothesis_groups:
    - canonical_alg12_cdg_model
    evidence:
    - reference: PMID:32530140
      reference_title: "ALG12-CDG: An unusual patient without intellectual disability and facial dysmorphism, and with a novel variant."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Increased levels of hypoglycosylated forms of F XI (also with
        significant deficiency) and transferrin were also detected.
      explanation: >-
        The patient finding supports hypoglycosylated and deficient factor XI as
        an intermediate to coagulation abnormality.
- name: Neurodevelopmental and brain involvement
  description: >-
    ALG12-CDG neurodevelopmental involvement includes developmental delay,
    intellectual disability, hypotonia, and reported brain anomalies.
  locations:
  - preferred_term: brain
    term:
      id: UBERON:0000955
      label: brain
  biological_processes:
  - preferred_term: nervous system development
    modifier: ABNORMAL
    term:
      id: GO:0007399
      label: nervous system development
  evidence:
  - reference: PMID:38717015
    reference_title: Expanded prenatal phenotype of ALG12-associated congenital disorder of glycosylation including bilateral multicystic kidneys.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Currently reported features of ALG12-CDG include: developmental delay,
      hypotonia, failure to thrive and/or short stature, brain anomalies,
      recurrent infections, hypogammaglobulinemia, coagulation abnormalities,
      and genitourinary abnormalities.
    explanation: >-
      The prenatal phenotype report summarizes the neurologic and brain feature
      set reported in ALG12-CDG.
  - reference: PMID:31481313
    reference_title: "Complex phenotypes in ALG12-congenital disorder of glycosylation (ALG12-CDG): Case series and review of the literature."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      ALG12-congenital disorder of glycosylation (ALG12-CDG) is a rare disorder
      caused by a deficiency of
      dolichol-P-mannose:Man7GlcNAc2-PP-dolichyl-α-6-mannosyltransferase which
      presents with intellectual disability, hypotonia, dysmorphic features, low
      IgG levels with recurrent infections, male genital hypoplasia, and
      coagulation abnormalities.
    explanation: >-
      The case-series abstract directly supports intellectual disability and
      hypotonia as neurologic manifestations.
  downstream:
  - target: Global developmental delay
    description: Developmental delay is part of the reported ALG12-CDG neurologic spectrum.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    hypothesis_groups:
    - canonical_alg12_cdg_model
    evidence:
    - reference: PMID:38717015
      reference_title: Expanded prenatal phenotype of ALG12-associated congenital disorder of glycosylation including bilateral multicystic kidneys.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Currently reported features of ALG12-CDG include: developmental delay,
        hypotonia, failure to thrive and/or short stature, brain anomalies,
        recurrent infections, hypogammaglobulinemia, coagulation abnormalities,
        and genitourinary abnormalities.
      explanation: The report lists developmental delay among ALG12-CDG features.
  - target: Intellectual disability
    description: Intellectual disability is part of the reported ALG12-CDG neurologic spectrum.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    hypothesis_groups:
    - canonical_alg12_cdg_model
    evidence:
    - reference: PMID:31481313
      reference_title: "Complex phenotypes in ALG12-congenital disorder of glycosylation (ALG12-CDG): Case series and review of the literature."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        ALG12-congenital disorder of glycosylation (ALG12-CDG) is a rare
        disorder caused by a deficiency of
        dolichol-P-mannose:Man7GlcNAc2-PP-dolichyl-α-6-mannosyltransferase
        which presents with intellectual disability, hypotonia, dysmorphic
        features, low IgG levels with recurrent infections, male genital
        hypoplasia, and coagulation abnormalities.
      explanation: The case-series abstract directly lists intellectual disability.
  - target: Hypotonia
    description: Hypotonia is part of the reported ALG12-CDG neurologic spectrum.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    hypothesis_groups:
    - canonical_alg12_cdg_model
    evidence:
    - reference: PMID:38717015
      reference_title: Expanded prenatal phenotype of ALG12-associated congenital disorder of glycosylation including bilateral multicystic kidneys.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Currently reported features of ALG12-CDG include: developmental delay,
        hypotonia, failure to thrive and/or short stature, brain anomalies,
        recurrent infections, hypogammaglobulinemia, coagulation abnormalities,
        and genitourinary abnormalities.
      explanation: The report lists hypotonia among ALG12-CDG features.
- name: Growth and feeding impairment
  description: >-
    ALG12-CDG can impair somatic growth and feeding, presenting as failure to
    thrive, growth retardation, anorexia, or short stature.
  evidence:
  - reference: PMID:12217961
    reference_title: ALG12 mannosyltransferase defect in congenital disorder of glycosylation type lg.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The severe disease was identified in a child presenting with psychomotor
      retardation, hypotonia, growth retardation, dysmorphic features and
      anorexia.
    explanation: >-
      The original report describes growth retardation and anorexia in an
      ALG12-CDG child.
  - reference: PMID:38717015
    reference_title: Expanded prenatal phenotype of ALG12-associated congenital disorder of glycosylation including bilateral multicystic kidneys.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Currently reported features of ALG12-CDG include: developmental delay,
      hypotonia, failure to thrive and/or short stature, brain anomalies,
      recurrent infections, hypogammaglobulinemia, coagulation abnormalities,
      and genitourinary abnormalities.
    explanation: >-
      The prenatal phenotype report summarizes failure to thrive and/or short
      stature in the broader ALG12-CDG phenotype.
  downstream:
  - target: Failure to thrive
    description: Failure to thrive is a reported growth manifestation of ALG12-CDG.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    hypothesis_groups:
    - canonical_alg12_cdg_model
    evidence:
    - reference: PMID:38717015
      reference_title: Expanded prenatal phenotype of ALG12-associated congenital disorder of glycosylation including bilateral multicystic kidneys.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Currently reported features of ALG12-CDG include: developmental delay,
        hypotonia, failure to thrive and/or short stature, brain anomalies,
        recurrent infections, hypogammaglobulinemia, coagulation abnormalities,
        and genitourinary abnormalities.
      explanation: The report lists failure to thrive among ALG12-CDG features.
  - target: Short stature
    description: Short stature is a reported growth manifestation of ALG12-CDG.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    hypothesis_groups:
    - canonical_alg12_cdg_model
    evidence:
    - reference: PMID:38717015
      reference_title: Expanded prenatal phenotype of ALG12-associated congenital disorder of glycosylation including bilateral multicystic kidneys.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Currently reported features of ALG12-CDG include: developmental delay,
        hypotonia, failure to thrive and/or short stature, brain anomalies,
        recurrent infections, hypogammaglobulinemia, coagulation abnormalities,
        and genitourinary abnormalities.
      explanation: The report lists short stature as a growth manifestation.
- name: Dysmorphic and genitourinary developmental involvement
  description: >-
    ALG12-CDG can involve craniofacial dysmorphism and male genitourinary
    developmental abnormalities.
  evidence:
  - reference: PMID:31481313
    reference_title: "Complex phenotypes in ALG12-congenital disorder of glycosylation (ALG12-CDG): Case series and review of the literature."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      ALG12-congenital disorder of glycosylation (ALG12-CDG) is a rare disorder
      caused by a deficiency of
      dolichol-P-mannose:Man7GlcNAc2-PP-dolichyl-α-6-mannosyltransferase which
      presents with intellectual disability, hypotonia, dysmorphic features, low
      IgG levels with recurrent infections, male genital hypoplasia, and
      coagulation abnormalities.
    explanation: >-
      The case-series abstract lists dysmorphic features and male genital
      hypoplasia in ALG12-CDG.
  - reference: CGGV:assertion_21631e85-8133-4703-a77c-c046effb6e56-2023-02-15T200000.000Z
    reference_title: "ALG12 / ALG12-congenital disorder of glycosylation (Definitive)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Common phenotypes include intellectual disability, hypotonia, dysmorphic
      features, coagulation abnormalities and genitourinary abnormalities.
    explanation: >-
      ClinGen independently lists dysmorphic and genitourinary abnormalities as
      common ALG12-CDG phenotypes.
  downstream:
  - target: Facial dysmorphism
    description: Dysmorphic features include craniofacial involvement.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    hypothesis_groups:
    - canonical_alg12_cdg_model
    evidence:
    - reference: PMID:31481313
      reference_title: "Complex phenotypes in ALG12-congenital disorder of glycosylation (ALG12-CDG): Case series and review of the literature."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        ALG12-congenital disorder of glycosylation (ALG12-CDG) is a rare
        disorder caused by a deficiency of
        dolichol-P-mannose:Man7GlcNAc2-PP-dolichyl-α-6-mannosyltransferase
        which presents with intellectual disability, hypotonia, dysmorphic
        features, low IgG levels with recurrent infections, male genital
        hypoplasia, and coagulation abnormalities.
      explanation: The case-series abstract lists dysmorphic features.
  - target: Hypoplastic male external genitalia
    description: Male genital hypoplasia is a genitourinary developmental manifestation.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    hypothesis_groups:
    - canonical_alg12_cdg_model
    evidence:
    - reference: PMID:31481313
      reference_title: "Complex phenotypes in ALG12-congenital disorder of glycosylation (ALG12-CDG): Case series and review of the literature."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        ALG12-congenital disorder of glycosylation (ALG12-CDG) is a rare
        disorder caused by a deficiency of
        dolichol-P-mannose:Man7GlcNAc2-PP-dolichyl-α-6-mannosyltransferase
        which presents with intellectual disability, hypotonia, dysmorphic
        features, low IgG levels with recurrent infections, male genital
        hypoplasia, and coagulation abnormalities.
      explanation: The case-series abstract lists male genital hypoplasia.
- name: Renal and skeletal developmental involvement
  description: >-
    Severe ALG12-CDG can involve prenatal renal malformation and
    skeletal-dysplasia-like abnormalities.
  locations:
  - preferred_term: kidney
    term:
      id: UBERON:0002113
      label: kidney
  - preferred_term: skeletal system
    term:
      id: UBERON:0001434
      label: skeletal system
  biological_processes:
  - preferred_term: kidney development
    modifier: ABNORMAL
    term:
      id: GO:0001822
      label: kidney development
  - preferred_term: skeletal system development
    modifier: ABNORMAL
    term:
      id: GO:0001501
      label: skeletal system development
  evidence:
  - reference: PMID:38717015
    reference_title: Expanded prenatal phenotype of ALG12-associated congenital disorder of glycosylation including bilateral multicystic kidneys.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      In addition, skeletal abnormalities resembling a skeletal dysplasia
      including shortened long bones and talipes equinovarus have been seen in
      more severe neonatal presentation of this disorder.
    explanation: >-
      The prenatal report supports skeletal-dysplasia-like abnormalities in
      severe neonatal ALG12-CDG.
  - reference: PMID:38717015
    reference_title: Expanded prenatal phenotype of ALG12-associated congenital disorder of glycosylation including bilateral multicystic kidneys.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We report on a case expanding the phenotype of ALG12-CDG to include
      bilateral, multicystic kidneys in a neonatal demise identified with
      homozygous pathogenic variants in the ALG12 gene at c.1001del
      (p.N334Tfs*15) through clinical trio exome sequencing.
    explanation: >-
      The case report directly supports multicystic renal malformation in a
      severe prenatal ALG12-CDG presentation.
  downstream:
  - target: Skeletal-dysplasia-like abnormalities
    description: Skeletal dysplasia-like abnormalities are part of the severe neonatal branch.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    hypothesis_groups:
    - severe_prenatal_renal_skeletal_model
    evidence:
    - reference: PMID:38717015
      reference_title: Expanded prenatal phenotype of ALG12-associated congenital disorder of glycosylation including bilateral multicystic kidneys.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        In addition, skeletal abnormalities resembling a skeletal dysplasia
        including shortened long bones and talipes equinovarus have been seen in
        more severe neonatal presentation of this disorder.
      explanation: The report directly supports skeletal dysplasia-like abnormalities.
  - target: Multicystic kidney dysplasia
    description: Multicystic kidneys expand the renal phenotype of severe ALG12-CDG.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    hypothesis_groups:
    - severe_prenatal_renal_skeletal_model
    evidence:
    - reference: PMID:38717015
      reference_title: Expanded prenatal phenotype of ALG12-associated congenital disorder of glycosylation including bilateral multicystic kidneys.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        We report on a case expanding the phenotype of ALG12-CDG to include
        bilateral, multicystic kidneys in a neonatal demise identified with
        homozygous pathogenic variants in the ALG12 gene at c.1001del
        (p.N334Tfs*15) through clinical trio exome sequencing.
      explanation: The case report directly supports multicystic kidney dysplasia.
- name: Adult cardioskeletal structural involvement
  description: >-
    A single exceptional adult had ventricular septal defect and severe
    scoliosis. Coexisting ALG6 and KMT2D variants confound attribution, so this
    node records a bounded clinical association rather than an established
    consequence of ALG12 deficiency.
  locations:
  - preferred_term: heart
    term:
      id: UBERON:0000948
      label: heart
  - preferred_term: skeletal system
    term:
      id: UBERON:0001434
      label: skeletal system
  evidence:
  - reference: PMID:32530140
    reference_title: "ALG12-CDG: An unusual patient without intellectual disability and facial dysmorphism, and with a novel variant."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We here present an intriguing patient with an exceptional phenotype:
      25-year-old women with a ventricular septal defect and severe idiopathic
      scoliosis but no facial dysmorphism, who dances as a professional, and has
      a University degree.
    explanation: >-
      The report establishes co-occurrence in one adult but only partially
      supports ALG12 attribution because other variants may contribute.
  downstream:
  - target: Ventricular septal defect
    description: >-
      Ventricular septal defect was reported in one exceptional adult, but
      attribution to ALG12 deficiency is unknown and confounded by coexisting
      ALG6 and KMT2D variants.
    causal_link_type: UNKNOWN
    hypothesis_groups:
    - exceptional_adult_cardioskeletal_model
    evidence:
    - reference: PMID:32530140
      reference_title: "ALG12-CDG: An unusual patient without intellectual disability and facial dysmorphism, and with a novel variant."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        We here present an intriguing patient with an exceptional phenotype:
        25-year-old women with a ventricular septal defect and severe idiopathic
        scoliosis but no facial dysmorphism, who dances as a professional, and
        has a University degree.
      explanation: >-
        The single-patient co-occurrence only partially supports this edge and
        does not establish attribution to ALG12 deficiency.
  - target: Scoliosis
    description: >-
      Severe scoliosis was reported in one exceptional adult, but attribution
      to ALG12 deficiency is unknown and confounded by coexisting ALG6 and
      KMT2D variants.
    causal_link_type: UNKNOWN
    hypothesis_groups:
    - exceptional_adult_cardioskeletal_model
    evidence:
    - reference: PMID:32530140
      reference_title: "ALG12-CDG: An unusual patient without intellectual disability and facial dysmorphism, and with a novel variant."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        We here present an intriguing patient with an exceptional phenotype:
        25-year-old women with a ventricular septal defect and severe idiopathic
        scoliosis but no facial dysmorphism, who dances as a professional, and
        has a University degree.
      explanation: >-
        The single-patient co-occurrence only partially supports this edge and
        does not establish attribution to ALG12 deficiency.
phenotypes:
- name: Global developmental delay
  category: Neurologic
  description: Developmental delay is a reported core feature of ALG12-CDG.
  phenotype_term:
    preferred_term: Global developmental delay
    term:
      id: HP:0001263
      label: Global developmental delay
  evidence:
  - reference: PMID:38717015
    reference_title: Expanded prenatal phenotype of ALG12-associated congenital disorder of glycosylation including bilateral multicystic kidneys.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Currently reported features of ALG12-CDG include: developmental delay,
      hypotonia, failure to thrive and/or short stature, brain anomalies,
      recurrent infections, hypogammaglobulinemia, coagulation abnormalities,
      and genitourinary abnormalities.
    explanation: >-
      The prenatal phenotype report summarizes developmental delay among
      reported ALG12-CDG features.
- name: Intellectual disability
  category: Neurologic
  description: Intellectual disability is a core neurodevelopmental phenotype in ALG12-CDG.
  phenotype_term:
    preferred_term: Intellectual disability
    term:
      id: HP:0001249
      label: Intellectual disability
  evidence:
  - reference: PMID:31481313
    reference_title: "Complex phenotypes in ALG12-congenital disorder of glycosylation (ALG12-CDG): Case series and review of the literature."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      ALG12-congenital disorder of glycosylation (ALG12-CDG) is a rare disorder
      caused by a deficiency of
      dolichol-P-mannose:Man7GlcNAc2-PP-dolichyl-α-6-mannosyltransferase which
      presents with intellectual disability, hypotonia, dysmorphic features, low
      IgG levels with recurrent infections, male genital hypoplasia, and
      coagulation abnormalities.
    explanation: >-
      The case-series abstract directly lists intellectual disability among
      ALG12-CDG presenting features.
  - reference: CGGV:assertion_21631e85-8133-4703-a77c-c046effb6e56-2023-02-15T200000.000Z
    reference_title: "ALG12 / ALG12-congenital disorder of glycosylation (Definitive)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Common phenotypes include intellectual disability, hypotonia, dysmorphic
      features, coagulation abnormalities and genitourinary abnormalities.
    explanation: >-
      ClinGen names intellectual disability as a common phenotype for this
      gene-disease assertion.
- name: Hypotonia
  category: Neurologic
  description: Hypotonia is a recurrent neurologic manifestation.
  phenotype_term:
    preferred_term: Hypotonia
    term:
      id: HP:0001252
      label: Hypotonia
  evidence:
  - reference: PMID:38717015
    reference_title: Expanded prenatal phenotype of ALG12-associated congenital disorder of glycosylation including bilateral multicystic kidneys.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Currently reported features of ALG12-CDG include: developmental delay,
      hypotonia, failure to thrive and/or short stature, brain anomalies,
      recurrent infections, hypogammaglobulinemia, coagulation abnormalities,
      and genitourinary abnormalities.
    explanation: The report lists hypotonia as a currently reported feature.
- name: Failure to thrive
  category: Growth
  description: Feeding and growth impairment can present as failure to thrive.
  phenotype_term:
    preferred_term: Failure to thrive
    term:
      id: HP:0001508
      label: Failure to thrive
  evidence:
  - reference: PMID:38717015
    reference_title: Expanded prenatal phenotype of ALG12-associated congenital disorder of glycosylation including bilateral multicystic kidneys.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Currently reported features of ALG12-CDG include: developmental delay,
      hypotonia, failure to thrive and/or short stature, brain anomalies,
      recurrent infections, hypogammaglobulinemia, coagulation abnormalities,
      and genitourinary abnormalities.
    explanation: The report lists failure to thrive among current features.
- name: Short stature
  category: Growth
  description: Short stature is part of the reported growth phenotype.
  phenotype_term:
    preferred_term: Short stature
    term:
      id: HP:0004322
      label: Short stature
  evidence:
  - reference: PMID:38717015
    reference_title: Expanded prenatal phenotype of ALG12-associated congenital disorder of glycosylation including bilateral multicystic kidneys.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Currently reported features of ALG12-CDG include: developmental delay,
      hypotonia, failure to thrive and/or short stature, brain anomalies,
      recurrent infections, hypogammaglobulinemia, coagulation abnormalities,
      and genitourinary abnormalities.
    explanation: The report lists short stature as an alternate growth manifestation.
- name: Recurrent infections
  category: Immune
  description: Recurrent infections reflect immune involvement.
  phenotype_term:
    preferred_term: Recurrent infections
    term:
      id: HP:0002719
      label: Recurrent infections
  evidence:
  - reference: PMID:38717015
    reference_title: Expanded prenatal phenotype of ALG12-associated congenital disorder of glycosylation including bilateral multicystic kidneys.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Currently reported features of ALG12-CDG include: developmental delay,
      hypotonia, failure to thrive and/or short stature, brain anomalies,
      recurrent infections, hypogammaglobulinemia, coagulation abnormalities,
      and genitourinary abnormalities.
    explanation: >-
      The report lists recurrent infections among the currently reported
      ALG12-CDG features without restricting them to a specific organ system.
- name: Facial dysmorphism
  category: Craniofacial
  description: Dysmorphic facial features are a common craniofacial manifestation.
  phenotype_term:
    preferred_term: Facial dysmorphism
    term:
      id: HP:0001999
      label: Abnormal facial shape
  evidence:
  - reference: PMID:31481313
    reference_title: "Complex phenotypes in ALG12-congenital disorder of glycosylation (ALG12-CDG): Case series and review of the literature."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      ALG12-congenital disorder of glycosylation (ALG12-CDG) is a rare disorder
      caused by a deficiency of
      dolichol-P-mannose:Man7GlcNAc2-PP-dolichyl-α-6-mannosyltransferase which
      presents with intellectual disability, hypotonia, dysmorphic features, low
      IgG levels with recurrent infections, male genital hypoplasia, and
      coagulation abnormalities.
    explanation: >-
      The case-series abstract explicitly lists dysmorphic features in
      ALG12-CDG.
  - reference: CGGV:assertion_21631e85-8133-4703-a77c-c046effb6e56-2023-02-15T200000.000Z
    reference_title: "ALG12 / ALG12-congenital disorder of glycosylation (Definitive)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Common phenotypes include intellectual disability, hypotonia, dysmorphic
      features, coagulation abnormalities and genitourinary abnormalities.
    explanation: >-
      ClinGen independently lists dysmorphic features as common in ALG12-CDG.
- name: Decreased circulating immunoglobulin concentration
  category: Immune
  description: Hypogammaglobulinemia or low serum immunoglobulins can occur.
  phenotype_term:
    preferred_term: Hypogammaglobulinemia
    term:
      id: HP:0004313
      label: Decreased circulating immunoglobulin concentration
  evidence:
  - reference: PMID:31529350
    reference_title: "ALG12-CDG: novel glycophenotype insights endorse the molecular defect."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      ALG12-CDG is a severe multisystem disease associated with low to
      deficient serum immunoglobulins and recurrent infections.
    explanation: The glycophenotype report directly supports low serum immunoglobulins.
- name: Abnormality of coagulation
  category: Hematologic
  description: ALG12-CDG can involve coagulation factor abnormalities.
  phenotype_term:
    preferred_term: Coagulation abnormalities
    term:
      id: HP:0001928
      label: Abnormality of coagulation
  evidence:
  - reference: PMID:38717015
    reference_title: Expanded prenatal phenotype of ALG12-associated congenital disorder of glycosylation including bilateral multicystic kidneys.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Currently reported features of ALG12-CDG include: developmental delay,
      hypotonia, failure to thrive and/or short stature, brain anomalies,
      recurrent infections, hypogammaglobulinemia, coagulation abnormalities,
      and genitourinary abnormalities.
    explanation: The case-series abstract lists coagulation abnormalities.
  - reference: PMID:32530140
    reference_title: "ALG12-CDG: An unusual patient without intellectual disability and facial dysmorphism, and with a novel variant."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Increased levels of hypoglycosylated forms of F XI (also with significant
      deficiency) and transferrin were also detected.
    explanation: >-
      The adult case demonstrates hypoglycosylation and deficiency of a
      coagulation factor.
- name: Hypoplastic male external genitalia
  category: Genitourinary
  description: Male genital hypoplasia is part of the reported ALG12-CDG genitourinary spectrum.
  phenotype_term:
    preferred_term: Male genital hypoplasia
    term:
      id: HP:0000050
      label: Hypoplastic male external genitalia
  evidence:
  - reference: PMID:31481313
    reference_title: "Complex phenotypes in ALG12-congenital disorder of glycosylation (ALG12-CDG): Case series and review of the literature."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      ALG12-congenital disorder of glycosylation (ALG12-CDG) is a rare disorder
      caused by a deficiency of
      dolichol-P-mannose:Man7GlcNAc2-PP-dolichyl-α-6-mannosyltransferase which
      presents with intellectual disability, hypotonia, dysmorphic features, low
      IgG levels with recurrent infections, male genital hypoplasia, and
      coagulation abnormalities.
    explanation: >-
      The Tahata case-series abstract directly lists male genital hypoplasia.
  - reference: CGGV:assertion_21631e85-8133-4703-a77c-c046effb6e56-2023-02-15T200000.000Z
    reference_title: "ALG12 / ALG12-congenital disorder of glycosylation (Definitive)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Common phenotypes include intellectual disability, hypotonia, dysmorphic
      features, coagulation abnormalities and genitourinary abnormalities.
    explanation: >-
      ClinGen supports genitourinary abnormalities as common in ALG12-CDG.
- name: Skeletal-dysplasia-like abnormalities
  category: Musculoskeletal
  description: >-
    Severe neonatal presentations can include shortened long bones, talipes
    equinovarus, and other skeletal abnormalities described as resembling a
    skeletal dysplasia.
  phenotype_term:
    preferred_term: Skeletal-dysplasia-like abnormalities
    term:
      id: HP:0000924
      label: Abnormality of the skeletal system
  evidence:
  - reference: PMID:38717015
    reference_title: Expanded prenatal phenotype of ALG12-associated congenital disorder of glycosylation including bilateral multicystic kidneys.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      In addition, skeletal abnormalities resembling a skeletal dysplasia
      including shortened long bones and talipes equinovarus have been seen in
      more severe neonatal presentation of this disorder.
    explanation: >-
      The prenatal phenotype report supports skeletal abnormalities resembling
      a dysplasia in severe neonatal ALG12-CDG without establishing a specific
      skeletal dysplasia diagnosis.
- name: Multicystic kidney dysplasia
  category: Renal
  description: Bilateral multicystic kidneys have been reported as an expanded prenatal phenotype.
  phenotype_term:
    preferred_term: Multicystic kidney dysplasia
    term:
      id: HP:0000003
      label: Multicystic kidney dysplasia
  evidence:
  - reference: PMID:38717015
    reference_title: Expanded prenatal phenotype of ALG12-associated congenital disorder of glycosylation including bilateral multicystic kidneys.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We report on a case expanding the phenotype of ALG12-CDG to include
      bilateral, multicystic kidneys in a neonatal demise identified with
      homozygous pathogenic variants in the ALG12 gene at c.1001del
      (p.N334Tfs*15) through clinical trio exome sequencing.
    explanation: >-
      This directly supports multicystic kidneys as a reported prenatal
      extension of the phenotype.
- name: Ventricular septal defect
  category: Cardiovascular
  description: >-
    Ventricular septal defect was reported in one unusually mild adult with an
    ALG12 variant and coexisting ALG6 and KMT2D variants, leaving attribution to
    ALG12-CDG uncertain.
  phenotype_term:
    preferred_term: Ventricular septal defect
    term:
      id: HP:0001629
      label: Ventricular septal defect
  evidence:
  - reference: PMID:32530140
    reference_title: "ALG12-CDG: An unusual patient without intellectual disability and facial dysmorphism, and with a novel variant."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We here present an intriguing patient with an exceptional phenotype:
      25-year-old women with a ventricular septal defect and severe idiopathic
      scoliosis but no facial dysmorphism, who dances as a professional, and
      has a University degree.
    explanation: >-
      The report establishes the single-patient co-occurrence but not that the
      ventricular septal defect was caused by ALG12 deficiency.
  - reference: PMID:32530140
    reference_title: "ALG12-CDG: An unusual patient without intellectual disability and facial dysmorphism, and with a novel variant."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      In this context, we wonder what the contribution, if any, may be of the
      coexisting KMT2D variants and of the ALG6 variant.
    explanation: >-
      The authors explicitly identify other-gene variants as possible modifiers
      of the exceptional adult phenotype.
- name: Scoliosis
  category: Musculoskeletal
  description: >-
    Severe scoliosis was reported in one unusually mild adult with an ALG12
    variant and coexisting ALG6 and KMT2D variants, leaving attribution to
    ALG12-CDG uncertain.
  phenotype_term:
    preferred_term: Scoliosis
    term:
      id: HP:0002650
      label: Scoliosis
  evidence:
  - reference: PMID:32530140
    reference_title: "ALG12-CDG: An unusual patient without intellectual disability and facial dysmorphism, and with a novel variant."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We here present an intriguing patient with an exceptional phenotype:
      25-year-old women with a ventricular septal defect and severe idiopathic
      scoliosis but no facial dysmorphism, who dances as a professional, and
      has a University degree.
    explanation: >-
      The report establishes the single-patient co-occurrence but not that the
      scoliosis was caused by ALG12 deficiency.
  - reference: PMID:32530140
    reference_title: "ALG12-CDG: An unusual patient without intellectual disability and facial dysmorphism, and with a novel variant."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      In this context, we wonder what the contribution, if any, may be of the
      coexisting KMT2D variants and of the ALG6 variant.
    explanation: >-
      The authors explicitly identify other-gene variants as possible modifiers
      of the exceptional adult phenotype.
biochemical:
- name: Type I transferrin hypoglycosylation pattern
  presence: Present
  specificity: Diagnostic support
  biomarker_term:
    preferred_term: N-glycan
    term:
      id: CHEBI:59520
      label: N-glycan
  readouts:
  - target: N-glycan precursor formation defect
    relationship: READOUT_OF
    direction: PRESENT_ABSENT
    endpoint_context: DIAGNOSTIC
    interpretation: >-
      A type I transferrin hypoglycosylation pattern reports impaired
      N-glycosylation-site occupancy downstream of the ALG12 precursor defect.
    evidence:
    - reference: PMID:31529350
      reference_title: "ALG12-CDG: novel glycophenotype insights endorse the molecular defect."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Intact serum transferrin showed, as expected for a CDG type I defect,
        underoccupancy of N-glycosylation sites.
      explanation: >-
        The patient-serum result directly supports transferrin underoccupancy as
        a readout of the precursor-assembly defect.
  evidence:
  - reference: PMID:34467644
    reference_title: A novel homozygous mutation in the human ALG12 gene results in an aberrant profile of oligomannose N-glycans in patient's serum.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Due to a newborn Slovak patient's clinical and biochemical abnormalities,
      the isoelectric focusing of transferrin was performed with observed
      significant hypoglycosylation typical of CDG I.
    explanation: >-
      This directly supports transferrin isoelectric focusing as a biochemical
      marker of type I CDG in ALG12-CDG.
- name: Aberrant serum oligomannose N-glycan profile
  presence: Present
  specificity: Diagnostic support
  biomarker_term:
    preferred_term: N-glycan
    term:
      id: CHEBI:59520
      label: N-glycan
  readouts:
  - target: ALG12 mannosyltransferase deficiency
    relationship: READOUT_OF
    direction: PRESENT_ABSENT
    endpoint_context: DIAGNOSTIC
    interpretation: >-
      Accumulation of GlcNAc2Man5-7 with reduced GlcNAc2Man8-9 reports impaired
      ALG12 enzymatic activity.
    evidence:
    - reference: PMID:34467644
      reference_title: A novel homozygous mutation in the human ALG12 gene results in an aberrant profile of oligomannose N-glycans in patient's serum.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Furthermore, analysis of neutral serum N-glycans by mass spectrometry
        revealed the accumulation of GlcNAc2Man5-7 and decreased levels of
        GlcNAc2Man8-9, which indicated impaired ALG12 enzymatic activity.
      explanation: >-
        The single-patient serum profile directly supports this readout of
        impaired ALG12 activity.
  evidence:
  - reference: PMID:34467644
    reference_title: A novel homozygous mutation in the human ALG12 gene results in an aberrant profile of oligomannose N-glycans in patient's serum.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Furthermore, analysis of neutral serum N-glycans by mass spectrometry
      revealed the accumulation of GlcNAc2Man5-7 and decreased levels of
      GlcNAc2Man8-9, which indicated impaired ALG12 enzymatic activity.
    explanation: >-
      Serum N-glycan profiling directly supports an ALG12-associated
      oligomannose signature.
- name: Hypoglycosylated antithrombin and factor XI
  presence: Present
  specificity: Supportive
  readouts:
  - target: Abnormal serum and IgG N-glycosylation
    relationship: READOUT_OF
    direction: PRESENT_ABSENT
    endpoint_context: DIAGNOSTIC
    interpretation: >-
      Hypoglycosylated coagulation proteins report systemic plasma-protein
      hypoglycosylation caused by the ALG12-CDG glycosylation defect.
    evidence:
    - reference: PMID:32530140
      reference_title: "ALG12-CDG: An unusual patient without intellectual disability and facial dysmorphism, and with a novel variant."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Increased levels of hypoglycosylated forms of F XI (also with
        significant deficiency) and transferrin were also detected.
      explanation: >-
        Detection of hypoglycosylated factor XI directly supports the
        plasma-protein hypoglycosylation readout.
  evidence:
  - reference: PMID:32530140
    reference_title: "ALG12-CDG: An unusual patient without intellectual disability and facial dysmorphism, and with a novel variant."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Congenital disorder of glycosylation diagnosis started through the
      identification of antithrombin deficiency without SERPINC1 defect and the
      detection of hypoglycosylated forms.
    explanation: >-
      The adult case shows a coagulation-protein hypoglycosylation clue to
      diagnosis.
  - reference: PMID:32530140
    reference_title: "ALG12-CDG: An unusual patient without intellectual disability and facial dysmorphism, and with a novel variant."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Increased levels of hypoglycosylated forms of F XI (also with significant
      deficiency) and transferrin were also detected.
    explanation: >-
      This directly supports hypoglycosylated and deficient factor XI in the
      reported patient.
genetic:
- name: ALG12
  association: Biallelic loss-of-function variants
  relationship_type: CAUSATIVE
  variant_origin: GERMLINE
  gene_term:
    preferred_term: ALG12
    term:
      id: hgnc:19358
      label: ALG12
  evidence:
  - reference: PMID:34467644
    reference_title: A novel homozygous mutation in the human ALG12 gene results in an aberrant profile of oligomannose N-glycans in patient's serum.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Genetic analysis of the coding regions of the ALG12 gene of the patient
      revealed a novel homozygous substitution mutation c.1439T>C
      p.(Leu480Pro) within Exon 10.
    explanation: >-
      The case report documents a homozygous ALG12 variant in an affected
      patient.
  - reference: PMID:38717015
    reference_title: Expanded prenatal phenotype of ALG12-associated congenital disorder of glycosylation including bilateral multicystic kidneys.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We report on a case expanding the phenotype of ALG12-CDG to include
      bilateral, multicystic kidneys in a neonatal demise identified with
      homozygous pathogenic variants in the ALG12 gene at c.1001del
      (p.N334Tfs*15) through clinical trio exome sequencing.
    explanation: >-
      The prenatal case report identifies a homozygous pathogenic ALG12
      frameshift variant.
  - reference: CGGV:assertion_21631e85-8133-4703-a77c-c046effb6e56-2023-02-15T200000.000Z
    reference_title: "ALG12 / ALG12-congenital disorder of glycosylation (Definitive)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      In summary, there is definitive evidence to support the relationship
      between ALG12 and autosomal recessive ALG12 -congenital disorder of
      glycosylation.
    explanation: >-
      ClinGen provides a deterministic structured assertion for the ALG12
      gene-disease relationship.
diagnosis:
- name: Transferrin isoelectric focusing screening
  description: >-
    Transferrin isoelectric focusing can detect a type I protein
    N-glycosylation pattern, but that pattern is shared across multiple CDG
    subtypes and does not identify ALG12-CDG by itself.
  diagnosis_term:
    preferred_term: clinical laboratory procedure
    term:
      id: NCIT:C25294
      label: Laboratory Procedure
  results: >-
    A type I transferrin hypoglycosylation pattern supports a disorder of early
    protein N-glycosylation and should prompt molecular subtype evaluation; it
    is not specific for ALG12-CDG.
  evidence:
  - reference: PMID:34467644
    reference_title: A novel homozygous mutation in the human ALG12 gene results in an aberrant profile of oligomannose N-glycans in patient's serum.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Due to a newborn Slovak patient's clinical and biochemical abnormalities,
      the isoelectric focusing of transferrin was performed with observed
      significant hypoglycosylation typical of CDG I.
    explanation: >-
      This patient result supports transferrin isoelectric focusing as a
      biochemical screen for a type I CDG pattern.
  - reference: PMID:31529350
    reference_title: "ALG12-CDG: novel glycophenotype insights endorse the molecular defect."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We analyzed serum native transferrin, as first line test for CDG
    explanation: >-
      This directly supports serum transferrin testing as a first-line CDG
      screen, without implying ALG12 specificity.
- name: Serum N-glycan profiling
  description: >-
    Mass-spectrometric serum N-glycan profiling identified an oligomannose
    pattern consistent with impaired ALG12 activity in one reported patient;
    its sensitivity and specificity as an ALG12-CDG diagnostic test are not
    established.
  diagnosis_term:
    preferred_term: clinical laboratory procedure
    term:
      id: NCIT:C25294
      label: Laboratory Procedure
  results: >-
    Accumulation of GlcNAc2Man5-7 with decreased GlcNAc2Man8-9 can provide
    supporting biochemical evidence for impaired ALG12 activity, but molecular
    confirmation is required.
  evidence:
  - reference: PMID:34467644
    reference_title: A novel homozygous mutation in the human ALG12 gene results in an aberrant profile of oligomannose N-glycans in patient's serum.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Furthermore, analysis of neutral serum N-glycans by mass spectrometry
      revealed the accumulation of GlcNAc2Man5-7 and decreased levels of
      GlcNAc2Man8-9, which indicated impaired ALG12 enzymatic activity.
    explanation: >-
      This single-patient result supports the reported ALG12-associated glycomic
      signature without establishing population-level diagnostic performance.
- name: ALG12 molecular genetic testing
  description: >-
    Molecular diagnosis is established by identifying biallelic pathogenic or
    likely pathogenic ALG12 variants; compound-heterozygous alleles should be
    shown or inferred to be in trans. Compatible glycosylation findings can
    support variant interpretation but are not themselves ALG12-specific.
  diagnosis_term:
    preferred_term: molecular genetic testing
    term:
      id: NCIT:C19770
      label: Molecular Analysis
  results: >-
    Homozygous or in-trans compound-heterozygous pathogenic or likely pathogenic
    ALG12 variants establish the molecular diagnosis; biochemical findings
    provide supporting pathway evidence.
  evidence:
  - reference: PMID:34467644
    reference_title: A novel homozygous mutation in the human ALG12 gene results in an aberrant profile of oligomannose N-glycans in patient's serum.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      This comprehensive genomic and glycomic approach led to the confirmation
      of the ALG12 pathogenic variant responsible for the clinical manifestation
      of the disorder in the patient described.
    explanation: >-
      The case report directly supports combined genomic and glycomic
      confirmation of the diagnosis.
  - reference: PMID:37644541
    reference_title: "Congenital disorders of glycosylation: narration of a story through its patents."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      CDG diagnosis has been at a rapid pace since the introduction of
      whole-exome/whole-genome sequencing as a diagnostic tool.
    explanation: >-
      This CDG-wide review supports genome-scale sequencing as a modern
      diagnostic approach for CDG; it is broader than ALG12-CDG alone.
treatments:
- name: Reported immunoglobulin infusions
  description: >-
    Some ALG12-CDG patients with low circulating immunoglobulins have received
    immunoglobulin infusions. A 2024 review describes the reported response as
    apparently unsuccessful, so this records observed treatment use rather than
    an established effective ALG12-CDG therapy.
  treatment_term:
    preferred_term: immunoglobulin infusion therapy
    term:
      id: NCIT:C62710
      label: Immunoglobulin Therapy
    therapeutic_agent:
    - preferred_term: Therapeutic Immune Globulin
      term:
        id: NCIT:C2701
        label: Therapeutic Immune Globulin
  target_phenotypes:
  - preferred_term: Hypogammaglobulinemia
    term:
      id: HP:0004313
      label: Decreased circulating immunoglobulin concentration
  - preferred_term: Recurrent infections
    term:
      id: HP:0002719
      label: Recurrent infections
  evidence:
  - reference: PMID:38550576
    reference_title: "Revisiting the immunopathology of congenital disorders of glycosylation: an updated review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      some ALG12-CDG patients have been treated with Ig infusions with apparent
      no success
    explanation: >-
      The review documents reported Ig-infusion use and apparent lack of success;
      it does not establish treatment benefit.
clinical_trials:
- name: NCT04199000
  status: RECRUITING
  description: >-
    Recruiting CDG-wide observational natural-history study relevant to broadly
    eligible, confirmed CDG subtypes such as ALG12-CDG. It is not an
    interventional trial and does not test ALG12-specific treatment efficacy.
  evidence:
  - reference: clinicaltrials:NCT04199000
    reference_title: Clinical and Basic Investigations Into Congenital Disorders of Glycosylation
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The purpose of this research is to study the natural history of
      congenital disorders of glycosylation and its causes and treatments.
    explanation: >-
      The study is CDG-wide and observational rather than an ALG12-specific
      efficacy trial, so the registry summary provides only partial support for
      ALG12-CDG relevance.
references:
- reference: PMID:12217961
  title: "ALG12 mannosyltransferase defect in congenital disorder of glycosylation type lg."
  findings: []
- reference: PMID:31481313
  title: "Complex phenotypes in ALG12-congenital disorder of glycosylation (ALG12-CDG): Case series and review of the literature."
  findings: []
- reference: PMID:31529350
  title: "ALG12-CDG: novel glycophenotype insights endorse the molecular defect."
  findings: []
- reference: PMID:32530140
  title: "ALG12-CDG: An unusual patient without intellectual disability and facial dysmorphism, and with a novel variant."
  findings: []
- reference: PMID:34467644
  title: "A novel homozygous mutation in the human ALG12 gene results in an aberrant profile of oligomannose N-glycans in patient's serum."
  findings: []
- reference: PMID:37644541
  title: "Congenital disorders of glycosylation: narration of a story through its patents."
  findings: []
- reference: PMID:38550576
  title: "Revisiting the immunopathology of congenital disorders of glycosylation: an updated review."
  findings: []
- reference: PMID:38717015
  title: "Expanded prenatal phenotype of ALG12-associated congenital disorder of glycosylation including bilateral multicystic kidneys."
  findings: []
- reference: CGGV:assertion_21631e85-8133-4703-a77c-c046effb6e56-2023-02-15T200000.000Z
  title: "ALG12 / ALG12-congenital disorder of glycosylation (Definitive)"
  findings: []
- reference: clinicaltrials:NCT04199000
  title: "Clinical and Basic Investigations Into Congenital Disorders of Glycosylation"
  findings: []
notes: >-
  Falcon deep research completed on 2026-05-10. The 2002 original ALG12-CDG
  abstract was fetched as PMID:12217961, and this curation uses fetched PubMed,
  ClinGen, and ClinicalTrials.gov caches with validator-checkable snippets.
datasets: []
📚

References & Deep Research

References

10
PMID:12217961
ALG12 mannosyltransferase defect in congenital disorder of glycosylation type lg.
No top-level findings curated for this source.
PMID:31481313
Complex phenotypes in ALG12-congenital disorder of glycosylation (ALG12-CDG): Case series and review of the literature.
No top-level findings curated for this source.
PMID:31529350
ALG12-CDG: novel glycophenotype insights endorse the molecular defect.
No top-level findings curated for this source.
PMID:32530140
ALG12-CDG: An unusual patient without intellectual disability and facial dysmorphism, and with a novel variant.
No top-level findings curated for this source.
PMID:34467644
A novel homozygous mutation in the human ALG12 gene results in an aberrant profile of oligomannose N-glycans in patient's serum.
No top-level findings curated for this source.
PMID:37644541
Congenital disorders of glycosylation: narration of a story through its patents.
No top-level findings curated for this source.
PMID:38550576
Revisiting the immunopathology of congenital disorders of glycosylation: an updated review.
No top-level findings curated for this source.
PMID:38717015
Expanded prenatal phenotype of ALG12-associated congenital disorder of glycosylation including bilateral multicystic kidneys.
No top-level findings curated for this source.
CGGV:assertion_21631e85-8133-4703-a77c-c046effb6e56-2023-02-15T200000.000Z
ALG12 / ALG12-congenital disorder of glycosylation (Definitive)
No top-level findings curated for this source.
clinicaltrials:NCT04199000
Clinical and Basic Investigations Into Congenital Disorders of Glycosylation
No top-level findings curated for this source.

Deep Research

1
Falcon ▸
ALG12–Congenital Disorder of Glycosylation (ALG12‑CDG; historical CDG‑Ig) — Disease Characteristics Research Report
Edison Scientific Literature 35 citations 2026-05-10T14:56:01.118066

ALG12–Congenital Disorder of Glycosylation (ALG12‑CDG; historical CDG‑Ig) — Disease Characteristics Research Report

Executive summary

ALG12‑CDG is a very rare autosomal recessive congenital disorder of glycosylation caused by deficiency of the ER luminal α1,6‑mannosyltransferase ALG12, which catalyzes addition of the 8th mannose during lipid‑linked oligosaccharide (LLO) assembly for protein N‑glycosylation. Biochemically it produces a type‑I carbohydrate‑deficient transferrin pattern and characteristic accumulation of truncated LLO/N‑glycans (notably Man7 intermediates and reduced Man8/Man9 species), with multisystem disease that often includes neurodevelopmental impairment, growth failure, dysmorphism, immunodeficiency (hypogammaglobulinemia), coagulation abnormalities, and variable severity up to early death. Recent (2023–2024) literature emphasizes accelerated CDG diagnosis via WES/WGS and emerging multi‑omics/proteomics tools, but also highlights the ongoing lack of targeted therapies for most CDGs, including ALG12‑CDG. (grubenmann2002alg12mannosyltransferasedefect pages 1-2, grubenmann2002alg12mannosyltransferasedefect pages 2-3, ziburova2021anovelhomozygous pages 1-1, monticelli2023congenitaldisordersof pages 1-2, pascoal2024revisitingtheimmunopathology pages 4-6)

Abbreviations

CDG: congenital disorder(s) of glycosylation; ER: endoplasmic reticulum; LLO: lipid‑linked oligosaccharide; Tf IEF: transferrin isoelectric focusing; MALDI‑TOF: matrix‑assisted laser desorption/ionization time‑of‑flight; MS: mass spectrometry; WES/WGS: whole‑exome/whole‑genome sequencing.

1. Disease information

1.1 What is the disease?

The first molecularly defined report described “a deficiency in the ALG12 ER α1,6‑mannosyltransferase resulting in a novel type of glycosylation disorder” and explicitly stated: “The ALG12 mannosyltransferase defect defines a new type of congenital disorder of glycosylation, designated CDG‑Ig.” (Grubenmann et al., 2002‑09; Human Molecular Genetics; DOI https://doi.org/10.1093/hmg/11.19.2331) (grubenmann2002alg12mannosyltransferasedefect pages 1-2)

A later case report defined the entity as: “Congenital disorder of glycosylation type Ig (ALG12‑CDG) is a rare inherited metabolic disease caused by a defect in alpha‑mannosyltransferase 8, encoded by the ALG12 gene (22q13.33).” (Ziburová et al., 2021‑09; American Journal of Medical Genetics A; DOI https://doi.org/10.1002/ajmg.a.62474) (ziburova2021anovelhomozygous pages 1-1)

1.2 Key identifiers

  • MONDO: MONDO_0011783 (“ALG12‑congenital disorder of glycosylation”) (OpenTargets disease identifier) (OpenTargets Search: ALG12-congenital disorder of glycosylation-ALG12)
  • OMIM/MIM: Literature excerpts report #607143 (ziburova2021anovelhomozygous pages 2-2, sturiale2019alg12cdgnovelglycophenotype pages 1-2); one excerpt reported OMIM: 607144 (tahata2019complexphenotypesin pages 1-2). These inconsistencies indicate that a direct OMIM lookup is recommended for knowledge‑base normalization.
  • Orphanet / ICD‑10 / ICD‑11 / MeSH: Not present in the retrieved full texts; would require direct lookup in those databases (limitation of current tool‑retrieved corpus).

1.3 Synonyms / alternative names

  • ALG12‑CDG (ziburova2021anovelhomozygous pages 1-1)
  • ALG12‑congenital disorder of glycosylation (ziburova2021anovelhomozygous pages 7-8)
  • CDG‑Ig (historical) (grubenmann2002alg12mannosyltransferasedefect pages 1-2)
  • “ALG12 mannosyltransferase defect” / “ALG12 α1,6‑mannosyltransferase deficiency” (functional descriptor) (grubenmann2002alg12mannosyltransferasedefect pages 1-2, sturiale2019alg12cdgnovelglycophenotype pages 1-2)

1.4 Evidence sources

Most disease‑specific information is derived from individual patient case reports/series plus aggregated reviews of CDG (e.g., immunopathology and diagnostic evolution). (grubenmann2002alg12mannosyltransferasedefect pages 1-2, tahata2019complexphenotypesin pages 1-2, monticelli2023congenitaldisordersof pages 1-2, pascoal2024revisitingtheimmunopathology pages 4-6)

2. Etiology

2.1 Disease causal factors

Primary cause (genetic): biallelic pathogenic variants in ALG12, encoding an ER mannosyltransferase involved in N‑glycan precursor assembly. (ziburova2021anovelhomozygous pages 2-2, grubenmann2002alg12mannosyltransferasedefect pages 1-2)

Mechanistic definition from a 2021 report: ALG12 encodes “the dolichyl‑P‑mannose Man‑7‑GlcNAc‑2‑PP‑dolichyl‑alpha‑6‑mannosyltransferase,” and “this enzyme transfers the eighth mannose residue from dolichyl‑P‑mannose to lipid‑linked oligosaccharides.” (Ziburová et al., 2021‑09; DOI https://doi.org/10.1002/ajmg.a.62474) (ziburova2021anovelhomozygous pages 2-2)

2.2 Risk factors

  • Genetic risk factors (causal variants): autosomal‑recessive inheritance; risk elevated in families with carrier parents and potentially consanguinity (not directly documented in retrieved excerpts). (ziburova2021anovelhomozygous pages 2-2)
  • Environmental risk factors: none established for causation in current evidence; clinical complications (e.g., infections) are downstream consequences.

2.3 Protective factors

No validated protective genetic or environmental factors were identified in the retrieved evidence.

2.4 Gene–environment interactions

Not specifically described for ALG12‑CDG in the retrieved evidence. In CDG more broadly, host glycan alterations may influence host–pathogen interactions, but ALG12‑specific GxE data were not retrieved. (pascoal2024revisitingtheimmunopathology pages 1-2)

3. Phenotypes (clinical features)

ALG12‑CDG presents as a multisystem disorder with marked inter‑individual variability.

3.1 Core phenotype spectrum (human evidence)

  • Neurodevelopmental: psychomotor delay/intellectual disability and hypotonia are prominent; the index case had “psychomotor retardation” and “hypotonia.” (grubenmann2002alg12mannosyltransferasedefect pages 1-2)
  • Growth / nutrition: growth retardation/failure to thrive, feeding problems/anorexia. (grubenmann2002alg12mannosyltransferasedefect pages 1-2, ziburova2021anovelhomozygous pages 5-5)
  • Craniofacial / dysmorphism: characteristic dysmorphism described across cases. (grubenmann2002alg12mannosyltransferasedefect pages 1-2, ziburova2021anovelhomozygous pages 5-5)
  • Immunologic / infection susceptibility: low immunoglobulins and recurrent infections; the index case had “markedly low immunoglobulins” and recurrent pneumonias requiring immunoglobulin infusions. (grubenmann2002alg12mannosyltransferasedefect pages 2-3)
  • Coagulation: low antithrombin and other coagulation factor abnormalities; e.g., low antithrombin reported in multiple cases. (grubenmann2002alg12mannosyltransferasedefect pages 2-3, sturiale2019alg12cdgnovelglycophenotype pages 6-8)
  • Genitourinary / endocrine‑related: male genital anomalies such as “micropenis” and undescended testes in the original case. (grubenmann2002alg12mannosyltransferasedefect pages 2-3)
  • Skeletal: skeletal abnormalities reported as frequent across published cases. (ziburova2021anovelhomozygous pages 5-5)

A 2021 synthesis of published cases reported frequent features including: “characteristic dysmorphism, psychomotor retardation, hypotonia, and/or skeletal abnormalities,” and also noted “feeding difficulties, respiratory distress, and frequent infections.” (Ziburová et al., 2021‑09; DOI https://doi.org/10.1002/ajmg.a.62474) (ziburova2021anovelhomozygous pages 5-5)

3.2 Age of onset, severity, progression

  • Onset is typically congenital/neonatal or early infancy, consistent with CDG type I disorders; a 2021 report describes evaluation in a “newborn” with significant biochemical abnormalities. (ziburova2021anovelhomozygous pages 1-1)
  • Severity is variable, ranging from severe infantile lethal multisystem disease to milder presentations; a 2019 case series described three brothers including one who “died at 18 months” and two survivors with comparatively milder disease. (tahata2019complexphenotypesin pages 1-2)

3.3 Quality of life impact

Direct QoL instrument data specific to ALG12‑CDG were not captured in the retrieved texts. Real‑world impact is inferred from multisystem disability (developmental delay, recurrent infections, feeding problems).

3.4 Suggested HPO terms (examples)

(ontology suggestions; not exhaustive) * Developmental delay — HP:0001263 * Intellectual disability — HP:0001249 * Hypotonia — HP:0001252 * Growth delay / failure to thrive — HP:0001508 / HP:0001507 * Microcephaly — HP:0000252 (reported in some cases) (sturiale2019alg12cdgnovelglycophenotype pages 6-8) * Recurrent respiratory infections — HP:0002205 (supported by recurrent pneumonias/infections) (grubenmann2002alg12mannosyltransferasedefect pages 2-3, ziburova2021anovelhomozygous pages 5-5) * Hypogammaglobulinemia — HP:0004313 (grubenmann2002alg12mannosyltransferasedefect pages 2-3, pascoal2024revisitingtheimmunopathology pages 4-6) * Abnormal coagulation / prolonged aPTT — HP:0011014 / HP:0030842 (sturiale2019alg12cdgnovelglycophenotype pages 6-8) * Cryptorchidism — HP:0000028; Micropenis — HP:0000054 (grubenmann2002alg12mannosyltransferasedefect pages 2-3)

4. Genetic / molecular information

4.1 Causal gene

  • ALG12 (approved symbol used in OpenTargets; Ensembl ENSG00000182858) (OpenTargets Search: ALG12-congenital disorder of glycosylation-ALG12)

4.2 Pathogenic variant classes (examples from primary reports)

Reported variants include missense, frameshift, and (in later literature) intronic splice‑altering variants; most evidence supports loss‑of‑function or hypomorphic loss‑of‑function. (grubenmann2002alg12mannosyltransferasedefect pages 1-2, tahata2019complexphenotypesin pages 1-2, ziburova2021anovelhomozygous pages 1-1)

Examples: * Compound heterozygous missense: T67M and R146Q in the first report. (grubenmann2002alg12mannosyltransferasedefect pages 1-2) * Frameshift: c.1001delA (p.N334TfsX15) reported in a family case series. (tahata2019complexphenotypesin pages 1-2) * Missense: c.1439T>C (p.Leu480Pro) reported as homozygous in a Slovak patient. (ziburova2021anovelhomozygous pages 1-1) * Compound heterozygous missense: c.367G>A (p.Gly123Arg) and c.1439T>C (p.Leu480Pro) in another patient. (sturiale2019alg12cdgnovelglycophenotype pages 6-8)

Population frequency note (limited): p.Leu480Pro was described as having a very low ExAC frequency (“8 × 10−6”). (sturiale2019alg12cdgnovelglycophenotype pages 6-8)

4.3 Modifier genes / epigenetics / chromosomal abnormalities

No ALG12‑CDG‑specific modifier genes, epigenetic mechanisms, or recurrent chromosomal abnormalities were identified in the retrieved texts.

5. Environmental information

ALG12‑CDG is a Mendelian disorder primarily driven by biallelic ALG12 variants; no consistent non‑genetic causal environmental exposures were identified.

6. Mechanism / pathophysiology

6.1 Causal chain (from gene defect to biochemical signature)

  1. ALG12 enzymatic defect in ER N‑glycan precursor assembly: ALG12 adds the 8th mannose residue during LLO synthesis. (ziburova2021anovelhomozygous pages 2-2, pascoal2024revisitingtheimmunopathology pages 4-6)
  2. Truncated LLO accumulation: patient fibroblasts showed accumulation of DolPP‑GlcNAc2Man7 and absence of mature DolPP‑GlcNAc2Man9Glc3. (grubenmann2002alg12mannosyltransferasedefect pages 2-3)
  3. Transfer of truncated glycans to proteins → hypoglycosylation: serum transferrin IEF shows a type‑I CDG pattern (decreased tetrasialotransferrin with increased disialo/asialo forms). (grubenmann2002alg12mannosyltransferasedefect pages 2-3)
  4. Systemic multisystem disease due to widespread hypoglycosylation affecting secreted and membrane proteins (neurodevelopment, immunity, coagulation, endocrine axes). (grubenmann2002alg12mannosyltransferasedefect pages 2-3, pascoal2024revisitingtheimmunopathology pages 4-6)

6.2 Biochemical abnormalities in serum glycomics

A 2021 report found MS evidence of impaired ALG12 activity: “analysis of neutral serum N‑glycans by mass spectrometry revealed the accumulation of GlcNAc2Man5–7 and decreased levels of GlcNAc2Man8–9.” (ziburova2021anovelhomozygous pages 1-1)

6.3 Immune involvement (expert synthesis)

A 2024 immunopathology review classifies ALG12‑CDG among “predominantly antibody deficiencies” characterized by “hypogammaglobulinemia and low IgG.” (Pascoal et al., 2024‑03; Frontiers in Immunology; DOI https://doi.org/10.3389/fimmu.2024.1350101) (pascoal2024revisitingtheimmunopathology pages 3-4, pascoal2024revisitingtheimmunopathology pages 4-6)

Mechanistic framing in the same review: defective glycosylation can lead to “defective antibody glycosylation,” reducing stability and Fc receptor binding, likely contributing to antibody deficiency and infection susceptibility. (pascoal2024revisitingtheimmunopathology pages 4-6)

6.4 Suggested GO / CL / pathway terms (examples)

  • GO Biological Process: protein N‑linked glycosylation; dolichol‑linked oligosaccharide biosynthetic process.
  • GO Cellular Component: endoplasmic reticulum membrane; ER lumen.
  • Cell Ontology (CL): B cell (CL:0000236), plasma cell (CL:0000786), hepatocyte (CL:0000182), neuron (CL:0000540) — reflecting immune, liver/coagulation, and neurodevelopmental involvement.
  • Reactome/KEGG pathway concept: N‑glycan precursor (LLO) biosynthesis in ER (ALG3/ALG9/ALG12 steps referenced in CDG literature). (pascoal2024revisitingtheimmunopathology pages 4-6)

7. Anatomical structures affected

Based on reported phenotypes and biochemical effects: * Central nervous system (neurodevelopmental delay, hypotonia) (UBERON:0000955 — brain) * Immune system (hypogammaglobulinemia, infections) (UBERON:0002405 — immune system) * Liver / plasma protein production (coagulation factors, antithrombin, transaminases) (UBERON:0002107 — liver) (grubenmann2002alg12mannosyltransferasedefect pages 2-3, ziburova2021anovelhomozygous pages 5-5) * Male reproductive system (micropenis, cryptorchidism) (UBERON:0000079 — male reproductive system) (grubenmann2002alg12mannosyltransferasedefect pages 2-3)

Subcellular localization relevant to mechanism: endoplasmic reticulum (GO:0005783) consistent with ER mannosyltransferase role and LLO assembly. (grubenmann2002alg12mannosyltransferasedefect pages 1-2, ziburova2021anovelhomozygous pages 2-2)

8. Temporal development

  • Typical onset: congenital/neonatal or infancy (newborn presentation and early‑life diagnosis described). (ziburova2021anovelhomozygous pages 1-1)
  • Course: variable; severe early fatal disease has been reported as well as longer survival with chronic multisystem impairment. (tahata2019complexphenotypesin pages 1-2, ziburova2021anovelhomozygous pages 5-5)

No formal staging system specific to ALG12‑CDG was identified.

9. Inheritance and population

9.1 Inheritance

Autosomal recessive, supported by homozygous and compound heterozygous cases. (ziburova2021anovelhomozygous pages 2-2, sturiale2019alg12cdgnovelglycophenotype pages 6-8)

9.2 Epidemiology

Robust incidence/prevalence estimates for ALG12‑CDG were not found in the retrieved evidence. However, multiple primary sources emphasize extreme rarity: * “To date, only 15 patients have been diagnosed with ALG12‑CDG globally.” (Ziburová et al., 2021‑09; DOI https://doi.org/10.1002/ajmg.a.62474) (ziburova2021anovelhomozygous pages 1-1) * Another excerpt states the Slovak case “brings the total number of published cases of this subtype to 16.” (ziburova2021anovelhomozygous pages 5-5)

10. Diagnostics

10.1 Clinical biochemical tests

Transferrin isoelectric focusing / carbohydrate‑deficient transferrin * Index case evidence: transferrin IEF demonstrated decreased tetrasialotransferrin with increased disialo/asialotransferrin (type‑I CDG pattern). (grubenmann2002alg12mannosyltransferasedefect pages 2-3)

Lipid‑linked oligosaccharide analysis (patient fibroblasts) * Demonstrated accumulation of truncated DolPP‑GlcNAc2Man7 and loss of mature DolPP‑GlcNAc2Man9Glc3. (grubenmann2002alg12mannosyltransferasedefect pages 2-3)

Serum N‑glycan profiling by MS * “Accumulation of GlcNAc2Man5–7 and decreased levels of GlcNAc2Man8–9” in neutral serum N‑glycans. (ziburova2021anovelhomozygous pages 1-1)

10.2 Genetic testing

Exome/genome sequencing is widely used for CDG diagnosis broadly. A 2023 review states: “CDG diagnosis has been at a rapid pace since the introduction of whole‑exome/whole‑genome sequencing as a diagnostic tool.” (Monticelli et al., 2023‑08; Orphanet J Rare Dis; DOI https://doi.org/10.1186/s13023-023-02852-w) (monticelli2023congenitaldisordersof pages 1-2)

The same review also emphasizes: “genetic analysis is the most reliable diagnostic.” (monticelli2023congenitaldisordersof pages 14-15)

10.3 Differential diagnosis

A comprehensive differential diagnosis list specific to ALG12‑CDG was not present in the retrieved texts. Practically, it overlaps with other CDG type I (LLO assembly/transfer) disorders, where transferrin IEF abnormalities prompt gene‑panel/WES/WGS confirmation.

11. Outcome / prognosis

Evidence indicates variable prognosis: * Severe early‑fatal multisystem disease is reported (e.g., infant death in a sibling group; fatal neonatal/infant outcomes in some cases). (tahata2019complexphenotypesin pages 1-2, ziburova2021anovelhomozygous pages 5-5) * Survivors can have chronic neurodevelopmental disability and recurrent infections. (tahata2019complexphenotypesin pages 1-2, grubenmann2002alg12mannosyltransferasedefect pages 2-3)

Quantitative survival curves or life expectancy estimates specific to ALG12‑CDG were not found in retrieved texts.

12. Treatment

12.1 Disease‑modifying therapy

No ALG12‑CDG‑specific disease‑modifying therapy was identified in the retrieved evidence.

12.2 Supportive and rehabilitative care (real‑world implementation)

  • Immunoglobulin replacement has been used in cases with hypogammaglobulinemia; the index case received “regular immunoglobulin infusions.” (grubenmann2002alg12mannosyltransferasedefect pages 2-3)
  • However, the 2024 immunopathology review notes that Ig infusion “attempts” in some ALG12‑CDG patients showed “apparent lack of success” (case‑dependent; limited published evidence). (pascoal2024revisitingtheimmunopathology pages 4-6)
  • Additional supportive management is implied by disease manifestations (infection management, nutritional support, coagulation monitoring).

Suggested MAXO terms (examples) * Immunoglobulin replacement therapy (MAXO term for IVIG/SCIG) * Anti‑infective therapy / infection prophylaxis * Nutritional support / enteral feeding * Coagulation factor replacement / management of coagulopathy * Physical therapy / occupational therapy / speech therapy for developmental impairment

12.3 Clinical trials

No interventional trials specific to ALG12‑CDG were found. A key real‑world research infrastructure is an observational CDG natural history study: * NCT04199000 (ClinicalTrials.gov; first posted 2019; recruiting): observational case‑only study with “genetically, enzymatically, or molecularly confirmed diagnosis of CDG or NGLY1 deficiency,” enrollment target 500; includes questionnaires, clinical exams, Nijmegen progression scale and PROMIS measures; allows biospecimen collection for biomarker/DNA studies. ALG12 is listed among keywords. URL: https://clinicaltrials.gov/study/NCT04199000 (NCT04199000 chunk 1, NCT04199000 chunk 2)

13. Prevention

No primary prevention exists for Mendelian ALG12‑CDG beyond reproductive and carrier testing strategies: * Carrier testing in at‑risk families (based on known familial variants) * Prenatal diagnosis / preimplantation genetic testing where appropriate

These approaches were not detailed in the retrieved corpus but follow standard practice for autosomal recessive disorders.

14. Other species / natural disease

No naturally occurring veterinary disease analogs for ALG12‑CDG were identified in the retrieved evidence.

15. Model organisms / experimental systems

Direct ALG12‑CDG functional modeling evidence in the retrieved corpus is limited but includes: * Yeast complementation/ortholog modeling: The original report used yeast functional complementation to show that ALG12 patient mutations fail to rescue an alg12 yeast mutant, supporting pathogenicity. (grubenmann2002alg12mannosyltransferasedefect pages 1-2)

No detailed mammalian or zebrafish ALG12‑specific in vivo phenotype data were retrieved in this tool run; therefore, this section should be revisited with dedicated model‑organism database searches (MGI/ZFIN/IMPC) if required.

Recent developments and latest research (prioritizing 2023–2024)

Diagnostic acceleration and unmet needs

A 2023 Orphanet Journal of Rare Diseases review (patent‑focused) summarizes the state of the field: * CDG comprises “more than 160” defects. (monticelli2023congenitaldisordersof pages 1-2) * “CDG diagnosis has been at a rapid pace since the introduction of whole‑exome/whole‑genome sequencing as a diagnostic tool.” (monticelli2023congenitaldisordersof pages 1-2) * Despite progress, “diagnostic tools, drugs, and biomarkers are still urgently needed.” (monticelli2023congenitaldisordersof pages 1-2)

Immune phenotype synthesis for ALG12‑CDG

A 2024 Frontiers in Immunology review places ALG12‑CDG into an inborn‑errors‑of‑immunity framing as predominantly antibody deficiency and discusses how glycosylation defects can compromise antibody properties and infection defense. (pascoal2024revisitingtheimmunopathology pages 3-4, pascoal2024revisitingtheimmunopathology pages 4-6)

Emerging translational methods

A 2024 targeted proteomics paper describes an MRM assay to quantify low‑abundance ER glycosyltransferases in CDG patient fibroblasts and explicitly situates ALG12 among the ER enzymes in the pathway context (“ALG3, ALG9, ALG12…”). This represents a real‑world implementation of quantitative proteomics for CDG mechanism and potentially diagnostics/biomarker development. (Lin et al., 2024‑01; Int J Mol Sci; DOI https://doi.org/10.3390/ijms25021191) (lin2024targetedproteomicsreveals pages 1-2)

Key statistics and data points (from retrieved studies)

  • Reported patient count: “only 15 patients” diagnosed globally by 2021; Slovak report increased published cases to 16. (ziburova2021anovelhomozygous pages 1-1, ziburova2021anovelhomozygous pages 5-5)
  • Characteristic serum N‑glycan shift: accumulation of GlcNAc2Man5–7 with decreased GlcNAc2Man8–9 (MS evidence). (ziburova2021anovelhomozygous pages 1-1)
  • Patent landscape (CDG, not ALG12‑specific): final list of 43 patents categorized into therapy (25), delivery (2), and diagnostics (17). (monticelli2023congenitaldisordersof pages 1-2)

Evidence organization artifact

The following table summarizes key facts for knowledge‑base ingestion:

Category Key findings (concise) Evidence type Primary citations (include PMID if available; otherwise DOI/URL)
Disease definition ALG12-congenital disorder of glycosylation (ALG12-CDG), historically CDG-Ig, is a rare type I CDG caused by deficiency of ALG12 ER α1,6-mannosyltransferase; severe multisystem disease with hypoglycosylation. OMIM/MIM reported in literature as #607143; one excerpt also cites OMIM:607144. Human case report, review Grubenmann et al., 2002, Hum Mol Genet, DOI: https://doi.org/10.1093/hmg/11.19.2331; Ziburová et al., 2021, AJMG A, DOI: https://doi.org/10.1002/ajmg.a.62474; Tahata et al., 2019, Mol Genet Metab, DOI: https://doi.org/10.1016/j.ymgme.2019.08.007 (grubenmann2002alg12mannosyltransferasedefect pages 1-2, ziburova2021anovelhomozygous pages 2-2, tahata2019complexphenotypesin pages 1-2)
Gene/enzyme function ALG12 encodes dolichol-P-mannose:Man7GlcNAc2-PP-dolichyl-α-6-mannosyltransferase / α-mannosyltransferase 8, which adds the 8th mannose to the lipid-linked oligosaccharide precursor during N-glycan biosynthesis in the ER. Human case report, review Grubenmann et al., 2002, DOI: https://doi.org/10.1093/hmg/11.19.2331; Ziburová et al., 2021, DOI: https://doi.org/10.1002/ajmg.a.62474; Pascoal et al., 2024, Front Immunol, DOI: https://doi.org/10.3389/fimmu.2024.1350101 (grubenmann2002alg12mannosyltransferasedefect pages 1-2, ziburova2021anovelhomozygous pages 2-2, pascoal2024revisitingtheimmunopathology pages 4-6)
Inheritance Autosomal recessive; reported in homozygous and compound heterozygous states. Human case report/series Ziburová et al., 2021, DOI: https://doi.org/10.1002/ajmg.a.62474; Tahata et al., 2019, DOI: https://doi.org/10.1016/j.ymgme.2019.08.007; Sturiale et al., 2019, DOI: https://doi.org/10.1007/s10719-019-09890-2 (ziburova2021anovelhomozygous pages 2-2, tahata2019complexphenotypesin pages 1-2, sturiale2019alg12cdgnovelglycophenotype pages 6-8)
Core phenotypes Commonly reported: psychomotor/intellectual delay, hypotonia, growth retardation/failure to thrive, microcephaly, dysmorphic facial features, recurrent infections, feeding difficulties, respiratory distress, skeletal abnormalities; variable severity including neonatal/infantile fatal cases and milder presentations. Human case report/series, review Grubenmann et al., 2002, DOI: https://doi.org/10.1093/hmg/11.19.2331; Tahata et al., 2019, DOI: https://doi.org/10.1016/j.ymgme.2019.08.007; Ziburová et al., 2021, DOI: https://doi.org/10.1002/ajmg.a.62474; de la Morena-Barrio et al., 2020, DOI: https://doi.org/10.1002/mgg3.1304 (grubenmann2002alg12mannosyltransferasedefect pages 1-2, tahata2019complexphenotypesin pages 1-2, ziburova2021anovelhomozygous pages 5-5)
Immune involvement Predominantly antibody deficiency phenotype: hypogammaglobulinemia/low IgG, recurrent severe bacterial or sinopulmonary infections, altered lymphocyte counts/dysfunction. 2024 review groups ALG12-CDG with predominantly antibody deficiencies. Human case report, review Grubenmann et al., 2002, DOI: https://doi.org/10.1093/hmg/11.19.2331; Pascoal et al., 2024, DOI: https://doi.org/10.3389/fimmu.2024.1350101; Ziburová et al., 2021, DOI: https://doi.org/10.1002/ajmg.a.62474 (grubenmann2002alg12mannosyltransferasedefect pages 2-3, pascoal2024revisitingtheimmunopathology pages 4-6, ziburova2021anovelhomozygous pages 6-7)
Coagulation/endocrine Reported coagulation abnormalities include low antithrombin III, prolonged APTT, decreased coagulation factors; endocrine/metabolic findings include undetectable IGF-1/IGF-BP3, hypoglycemia, low cholesterol, elevated transaminases, and male genital anomalies (micropenis/cryptorchidism). Human case report/series Grubenmann et al., 2002, DOI: https://doi.org/10.1093/hmg/11.19.2331; Sturiale et al., 2019, DOI: https://doi.org/10.1007/s10719-019-09890-2; Ziburová et al., 2021, DOI: https://doi.org/10.1002/ajmg.a.62474; Tahata et al., 2019, DOI: https://doi.org/10.1016/j.ymgme.2019.08.007 (grubenmann2002alg12mannosyltransferasedefect pages 2-3, sturiale2019alg12cdgnovelglycophenotype pages 6-8, ziburova2021anovelhomozygous pages 5-5, tahata2019complexphenotypesin pages 1-2)
Diagnostics (transferrin IEF, LLO, serum N-glycan MS) Serum transferrin IEF shows a type I CDG pattern with decreased tetrasialotransferrin and increased disialo-/asialotransferrin. Patient fibroblasts can show truncated LLO with accumulation of DolPP-GlcNAc2Man7 and absence/reduction of mature DolPP-GlcNAc2Man9Glc3. Serum N-glycan MS/MALDI-TOF shows accumulation of GlcNAc2Man5-7 with decreased GlcNAc2Man8-9; transferrin/total serum glycomics can reveal mono-glycosylated transferrin and increased high-mannose/hybrid glycans. Human case report/series Grubenmann et al., 2002, DOI: https://doi.org/10.1093/hmg/11.19.2331; Ziburová et al., 2021, DOI: https://doi.org/10.1002/ajmg.a.62474; Sturiale et al., 2019, DOI: https://doi.org/10.1007/s10719-019-09890-2 (grubenmann2002alg12mannosyltransferasedefect pages 2-3, ziburova2021anovelhomozygous pages 1-1, sturiale2019alg12cdgnovelglycophenotype pages 6-8)
Variant examples Reported pathogenic/likely pathogenic examples include compound heterozygous p.T67M and p.R146Q; c.1001delA (p.N334Tfs*15) with c.671C>T (p.T224M, reported as VUS in one series); c.367G>A (p.Gly123Arg) and c.1439T>C (p.Leu480Pro); homozygous c.1439T>C (p.Leu480Pro); novel p.Val26Asp. 2025 report (outside requested priority window) adds an intronic splice variant upstream of exon 2. Human case report/series Grubenmann et al., 2002, DOI: https://doi.org/10.1093/hmg/11.19.2331; Tahata et al., 2019, DOI: https://doi.org/10.1016/j.ymgme.2019.08.007; Sturiale et al., 2019, DOI: https://doi.org/10.1007/s10719-019-09890-2; Ziburová et al., 2021, DOI: https://doi.org/10.1002/ajmg.a.62474 (grubenmann2002alg12mannosyltransferasedefect pages 1-2, tahata2019complexphenotypesin pages 1-2, sturiale2019alg12cdgnovelglycophenotype pages 6-8, ziburova2021anovelhomozygous pages 1-1)
Epidemiology/patient counts Extremely rare. Literature excerpts report “only 15 patients” worldwide by 2021 and “16 published cases” after the Slovak case; no robust prevalence/incidence estimate identified in available context. Human case report, review Ziburová et al., 2021, DOI: https://doi.org/10.1002/ajmg.a.62474; Piedade et al., 2022, J Rare Dis, DOI: https://doi.org/10.1007/s44162-022-00003-6 (ziburova2021anovelhomozygous pages 1-1, ziburova2021anovelhomozygous pages 5-5)
Management/supportive care No disease-specific curative therapy identified in available context. Supportive care includes immunoglobulin replacement/IVIG in patients with hypogammaglobulinemia, management of infections, nutritional/supportive multidisciplinary care, and monitoring of coagulation/endocrine issues. Reported response to Ig infusion may be variable or limited in some ALG12-CDG cases. Human case report, review Grubenmann et al., 2002, DOI: https://doi.org/10.1093/hmg/11.19.2331; Pascoal et al., 2024, DOI: https://doi.org/10.3389/fimmu.2024.1350101 (grubenmann2002alg12mannosyltransferasedefect pages 2-3, pascoal2024revisitingtheimmunopathology pages 4-6)
Research/real-world implementations Real-world diagnosis increasingly uses WES/WGS for CDG discovery/confirmation; MS-based glycomics (MALDI-MS/UHPLC-ESI-MS) refines subtype-specific glycophenotypes; targeted proteomics/MRM assays for ER glycosyltransferases were introduced in 2024 and include the ALG12 pathway, supporting translational diagnostics/research. Patent review notes CDG diagnosis accelerated with WES/WGS and that diagnostic tools, drugs, and biomarkers remain urgently needed. Review, translational research Monticelli et al., 2023, DOI: https://doi.org/10.1186/s13023-023-02852-w; Sturiale et al., 2019, DOI: https://doi.org/10.1007/s10719-019-09890-2; Lin et al., 2024, DOI: https://doi.org/10.3390/ijms25021191 (monticelli2023congenitaldisordersof pages 1-2, sturiale2019alg12cdgnovelglycophenotype pages 1-2, lin2024targetedproteomicsreveals pages 1-2)
Clinical trial registry (NCT04199000) Ongoing observational natural-history study: “Clinical and Basic Investigations Into Congenital Disorders of Glycosylation” (NCT04199000), recruiting, case-only, target enrollment 500, includes genetically/enzymatically/molecularly confirmed CDG or NGLY1 deficiency; outcomes include disease severity/progression measures and biomarker collection. ALG12 is listed among keywords, making the registry relevant to ALG12-CDG. Trial registry ClinicalTrials.gov NCT04199000: https://clinicaltrials.gov/study/NCT04199000 (NCT04199000 chunk 1, NCT04199000 chunk 2)

Table: This table summarizes key disease facts, clinical and molecular findings, diagnostics, management, and current research implementations for ALG12-CDG using only evidence available in the conversation context. It is designed for rapid knowledge-base ingestion with source-linked citations.

Limitations of this report (from available tool‑retrieved corpus)

  1. PMIDs were not available in the retrieved text snippets for several primary papers (DOIs/URLs were available); therefore, PMID‑level citation could not be consistently provided.
  2. Orphanet/ICD/MeSH identifiers were not present in the retrieved full texts; normalization would require direct database queries.
  3. Quantitative phenotype frequencies (percentages across cohorts) are largely unavailable because ALG12‑CDG literature is dominated by small case reports/series.
  4. Animal model phenotype data specific to ALG12 were not retrieved beyond yeast complementation.

Source URLs and publication dates (high‑priority items)

  • Grubenmann et al., “ALG12 mannosyltransferase defect in congenital disorder of glycosylation type Ig.” Human Molecular Genetics. 2002‑09. https://doi.org/10.1093/hmg/11.19.2331 (grubenmann2002alg12mannosyltransferasedefect pages 1-2)
  • Ziburová et al., “A novel homozygous mutation in the human ALG12 gene…” American Journal of Medical Genetics A. 2021‑09. https://doi.org/10.1002/ajmg.a.62474 (ziburova2021anovelhomozygous pages 1-1)
  • Monticelli et al., “Congenital disorders of glycosylation: narration of a story through its patents.” Orphanet J Rare Dis. 2023‑08. https://doi.org/10.1186/s13023-023-02852-w (monticelli2023congenitaldisordersof pages 1-2)
  • Pascoal et al., “Revisiting the immunopathology of congenital disorders of glycosylation: an updated review.” Frontiers in Immunology. 2024‑03. https://doi.org/10.3389/fimmu.2024.1350101 (pascoal2024revisitingtheimmunopathology pages 1-2)
  • Lin et al., “Targeted Proteomics Reveals Quantitative Differences…” Int J Mol Sci. 2024‑01. https://doi.org/10.3390/ijms25021191 (lin2024targetedproteomicsreveals pages 1-2)
  • ClinicalTrials.gov natural history study: NCT04199000. First posted 2019; recruiting. https://clinicaltrials.gov/study/NCT04199000 (NCT04199000 chunk 1)

References

  1. (grubenmann2002alg12mannosyltransferasedefect pages 1-2): C. Grubenmann, C. Frank, S. Kjaergaard, E. Berger, M. Aebi, and T. Hennet. Alg12 mannosyltransferase defect in congenital disorder of glycosylation type lg. Human molecular genetics, 11 19:2331-9, Sep 2002. URL: https://doi.org/10.1093/hmg/11.19.2331, doi:10.1093/hmg/11.19.2331. This article has 103 citations and is from a domain leading peer-reviewed journal.

  2. (grubenmann2002alg12mannosyltransferasedefect pages 2-3): C. Grubenmann, C. Frank, S. Kjaergaard, E. Berger, M. Aebi, and T. Hennet. Alg12 mannosyltransferase defect in congenital disorder of glycosylation type lg. Human molecular genetics, 11 19:2331-9, Sep 2002. URL: https://doi.org/10.1093/hmg/11.19.2331, doi:10.1093/hmg/11.19.2331. This article has 103 citations and is from a domain leading peer-reviewed journal.

  3. (ziburova2021anovelhomozygous pages 1-1): Jana Ziburová, Marek Nemčovič, Sergej Šesták, Jana Bellová, Zuzana Pakanová, Barbara Siváková, Anna Šalingová, Claudia Šebová, Mária Ostrožlíková, Dimitra‐Evanthia Lekka, Jana Brucknerová, Ingrid Brucknerová, Martina Skokňová, Alexandra Mc Cullough, Gabriela Hrčková, Anna Hlavatá, Vladimír Bzdúch, Ján Mucha, and Peter Baráth. A novel homozygous mutation in the human alg12 gene results in an aberrant profile of oligomannose n‐glycans in patient's serum. American Journal of Medical Genetics. Part a, 185:3494-3501, Sep 2021. URL: https://doi.org/10.1002/ajmg.a.62474, doi:10.1002/ajmg.a.62474. This article has 17 citations and is from a peer-reviewed journal.

  4. (monticelli2023congenitaldisordersof pages 1-2): Maria Monticelli, Tania D’Onofrio, Jaak Jaeken, Eva Morava, Giuseppina Andreotti, and Maria Vittoria Cubellis. Congenital disorders of glycosylation: narration of a story through its patents. Orphanet Journal of Rare Diseases, Aug 2023. URL: https://doi.org/10.1186/s13023-023-02852-w, doi:10.1186/s13023-023-02852-w. This article has 19 citations and is from a peer-reviewed journal.

  5. (pascoal2024revisitingtheimmunopathology pages 4-6): Carlota Pascoal, Rita Francisco, Patrícia Mexia, Beatriz Luís Pereira, Pedro Granjo, Helena Coelho, Mariana Barbosa, Vanessa dos Reis Ferreira, and Paula Alexandra Videira. Revisiting the immunopathology of congenital disorders of glycosylation: an updated review. Frontiers in Immunology, Mar 2024. URL: https://doi.org/10.3389/fimmu.2024.1350101, doi:10.3389/fimmu.2024.1350101. This article has 15 citations and is from a peer-reviewed journal.

  6. (OpenTargets Search: ALG12-congenital disorder of glycosylation-ALG12): Open Targets Query (ALG12-congenital disorder of glycosylation-ALG12, 2 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.

  7. (ziburova2021anovelhomozygous pages 2-2): Jana Ziburová, Marek Nemčovič, Sergej Šesták, Jana Bellová, Zuzana Pakanová, Barbara Siváková, Anna Šalingová, Claudia Šebová, Mária Ostrožlíková, Dimitra‐Evanthia Lekka, Jana Brucknerová, Ingrid Brucknerová, Martina Skokňová, Alexandra Mc Cullough, Gabriela Hrčková, Anna Hlavatá, Vladimír Bzdúch, Ján Mucha, and Peter Baráth. A novel homozygous mutation in the human alg12 gene results in an aberrant profile of oligomannose n‐glycans in patient's serum. American Journal of Medical Genetics. Part a, 185:3494-3501, Sep 2021. URL: https://doi.org/10.1002/ajmg.a.62474, doi:10.1002/ajmg.a.62474. This article has 17 citations and is from a peer-reviewed journal.

  8. (sturiale2019alg12cdgnovelglycophenotype pages 1-2): Luisa Sturiale, Sebastiano Bianca, Domenico Garozzo, Alessandra Terracciano, Emanuele Agolini, Angela Messina, Angelo Palmigiano, Francesca Esposito, Chiara Barone, Antonio Novelli, Agata Fiumara, Jaak Jaeken, and Rita Barone. Alg12-cdg: novel glycophenotype insights endorse the molecular defect. Glycoconjugate Journal, 36:461-472, Sep 2019. URL: https://doi.org/10.1007/s10719-019-09890-2, doi:10.1007/s10719-019-09890-2. This article has 22 citations and is from a peer-reviewed journal.

  9. (tahata2019complexphenotypesin pages 1-2): Shawn Tahata, Lauren B. Gunderson, Brendan Lanpher, and E. Morava. Complex phenotypes in alg12-congenital disorder of glycosylation (alg12-cdg): case series and review of the literature. Molecular genetics and metabolism, 128:409-414, Dec 2019. URL: https://doi.org/10.1016/j.ymgme.2019.08.007, doi:10.1016/j.ymgme.2019.08.007. This article has 25 citations and is from a peer-reviewed journal.

  10. (ziburova2021anovelhomozygous pages 7-8): Jana Ziburová, Marek Nemčovič, Sergej Šesták, Jana Bellová, Zuzana Pakanová, Barbara Siváková, Anna Šalingová, Claudia Šebová, Mária Ostrožlíková, Dimitra‐Evanthia Lekka, Jana Brucknerová, Ingrid Brucknerová, Martina Skokňová, Alexandra Mc Cullough, Gabriela Hrčková, Anna Hlavatá, Vladimír Bzdúch, Ján Mucha, and Peter Baráth. A novel homozygous mutation in the human alg12 gene results in an aberrant profile of oligomannose n‐glycans in patient's serum. American Journal of Medical Genetics. Part a, 185:3494-3501, Sep 2021. URL: https://doi.org/10.1002/ajmg.a.62474, doi:10.1002/ajmg.a.62474. This article has 17 citations and is from a peer-reviewed journal.

  11. (pascoal2024revisitingtheimmunopathology pages 1-2): Carlota Pascoal, Rita Francisco, Patrícia Mexia, Beatriz Luís Pereira, Pedro Granjo, Helena Coelho, Mariana Barbosa, Vanessa dos Reis Ferreira, and Paula Alexandra Videira. Revisiting the immunopathology of congenital disorders of glycosylation: an updated review. Frontiers in Immunology, Mar 2024. URL: https://doi.org/10.3389/fimmu.2024.1350101, doi:10.3389/fimmu.2024.1350101. This article has 15 citations and is from a peer-reviewed journal.

  12. (ziburova2021anovelhomozygous pages 5-5): Jana Ziburová, Marek Nemčovič, Sergej Šesták, Jana Bellová, Zuzana Pakanová, Barbara Siváková, Anna Šalingová, Claudia Šebová, Mária Ostrožlíková, Dimitra‐Evanthia Lekka, Jana Brucknerová, Ingrid Brucknerová, Martina Skokňová, Alexandra Mc Cullough, Gabriela Hrčková, Anna Hlavatá, Vladimír Bzdúch, Ján Mucha, and Peter Baráth. A novel homozygous mutation in the human alg12 gene results in an aberrant profile of oligomannose n‐glycans in patient's serum. American Journal of Medical Genetics. Part a, 185:3494-3501, Sep 2021. URL: https://doi.org/10.1002/ajmg.a.62474, doi:10.1002/ajmg.a.62474. This article has 17 citations and is from a peer-reviewed journal.

  13. (sturiale2019alg12cdgnovelglycophenotype pages 6-8): Luisa Sturiale, Sebastiano Bianca, Domenico Garozzo, Alessandra Terracciano, Emanuele Agolini, Angela Messina, Angelo Palmigiano, Francesca Esposito, Chiara Barone, Antonio Novelli, Agata Fiumara, Jaak Jaeken, and Rita Barone. Alg12-cdg: novel glycophenotype insights endorse the molecular defect. Glycoconjugate Journal, 36:461-472, Sep 2019. URL: https://doi.org/10.1007/s10719-019-09890-2, doi:10.1007/s10719-019-09890-2. This article has 22 citations and is from a peer-reviewed journal.

  14. (pascoal2024revisitingtheimmunopathology pages 3-4): Carlota Pascoal, Rita Francisco, Patrícia Mexia, Beatriz Luís Pereira, Pedro Granjo, Helena Coelho, Mariana Barbosa, Vanessa dos Reis Ferreira, and Paula Alexandra Videira. Revisiting the immunopathology of congenital disorders of glycosylation: an updated review. Frontiers in Immunology, Mar 2024. URL: https://doi.org/10.3389/fimmu.2024.1350101, doi:10.3389/fimmu.2024.1350101. This article has 15 citations and is from a peer-reviewed journal.

  15. (monticelli2023congenitaldisordersof pages 14-15): Maria Monticelli, Tania D’Onofrio, Jaak Jaeken, Eva Morava, Giuseppina Andreotti, and Maria Vittoria Cubellis. Congenital disorders of glycosylation: narration of a story through its patents. Orphanet Journal of Rare Diseases, Aug 2023. URL: https://doi.org/10.1186/s13023-023-02852-w, doi:10.1186/s13023-023-02852-w. This article has 19 citations and is from a peer-reviewed journal.

  16. (NCT04199000 chunk 1): Eva Morava-Kozicz. Clinical and Basic Investigations Into Congenital Disorders of Glycosylation. Icahn School of Medicine at Mount Sinai. 2019. ClinicalTrials.gov Identifier: NCT04199000

  17. (NCT04199000 chunk 2): Eva Morava-Kozicz. Clinical and Basic Investigations Into Congenital Disorders of Glycosylation. Icahn School of Medicine at Mount Sinai. 2019. ClinicalTrials.gov Identifier: NCT04199000

  18. (lin2024targetedproteomicsreveals pages 1-2): Qingsong Lin, Lei Zhou, Chuen Lam, Roman Sakson, Lars Beedgen, Patrick Bernhard, K. M. Alp, Nicole Lübbehusen, R. Röth, Beate Niesler, Marcin Luzarowski, Olga Shevchuk, Matthias P. Mayer, Christian Thiel, and Thomas Ruppert. Targeted proteomics reveals quantitative differences in low-abundance glycosyltransferases of patients with congenital disorders of glycosylation. International Journal of Molecular Sciences, 25:1191, Jan 2024. URL: https://doi.org/10.3390/ijms25021191, doi:10.3390/ijms25021191. This article has 5 citations.

  19. (ziburova2021anovelhomozygous pages 6-7): Jana Ziburová, Marek Nemčovič, Sergej Šesták, Jana Bellová, Zuzana Pakanová, Barbara Siváková, Anna Šalingová, Claudia Šebová, Mária Ostrožlíková, Dimitra‐Evanthia Lekka, Jana Brucknerová, Ingrid Brucknerová, Martina Skokňová, Alexandra Mc Cullough, Gabriela Hrčková, Anna Hlavatá, Vladimír Bzdúch, Ján Mucha, and Peter Baráth. A novel homozygous mutation in the human alg12 gene results in an aberrant profile of oligomannose n‐glycans in patient's serum. American Journal of Medical Genetics. Part a, 185:3494-3501, Sep 2021. URL: https://doi.org/10.1002/ajmg.a.62474, doi:10.1002/ajmg.a.62474. This article has 17 citations and is from a peer-reviewed journal.