MOGS-Congenital Disorder of Glycosylation (MOGS-CDG / CDG-IIb): Comprehensive Disease Characteristics Report

MONDO: MONDO:0011629 | Category: Mendelian (autosomal recessive inborn error of metabolism) Prepared: Iterations 1–5 — evidence base combines primary literature (human clinical case series and mechanistic studies) with live public-database queries (gnomAD constraint, ClinVar variant spectrum, UniProt protein architecture, ClinicalTrials.gov). MOGS-CDG is ultra-rare (~30 patients reported worldwide as of 2024), so most clinical evidence is from individual patients and small case series rather than aggregated registry-scale data.

Evidence provenance (database queries performed): gnomAD (constraint: pLI ≈ 0, LOEUF = 0.84 → LoF-tolerant, recessive) · ClinVar (647 MOGS records; ≈27 P/LP vs 153 VUS; overwhelmingly SNVs) · UniProt Q13724 (837-aa type II ER membrane GH63 enzyme; catalytic D583/E807; N-glycosylated at N657) · ClinicalTrials.gov (no MOGS-CDG-specific interventional trials). Evidence types are labelled throughout as human-clinical, in vitro, model-organism, or computational/database.

1. Disease Information

Overview. MOGS-CDG is an ultra-rare autosomal recessive congenital disorder of glycosylation caused by biallelic loss-of-function variants in MOGS, which encodes mannosyl-oligosaccharide glucosidase (glucosidase I / GCS1), the first enzyme in the endoplasmic-reticulum (ER) processing/trimming of N-linked oligosaccharides. Loss of glucosidase I activity blocks the initial trimming of the Glc₃Man₉GlcNAc₂ N-glycan precursor, disrupting N-glycan maturation on many glycoproteins. It is classified as a CDG type II (a defect of glycan processing/remodeling, as opposed to type I assembly defects). The first patient was described by De Praeter et al. in 2000 (10788335).

Key identifiers: - OMIM: #606056 (Congenital disorder of glycosylation, type IIb) — gene MOGS OMIM 601336 - Orphanet: ORPHA:79328 (MOGS-CDG / CDG-IIb) - Mondo: MONDO:0011629 - ICD-10: E77.8 (other disorders of glycoprotein metabolism); ICD-11: 5C51.2 (disorders of N-glycosylation) - MeSH: Congenital Disorders of Glycosylation (D018981) - Gene HGNC: MOGS (HGNC:24862); UniProt Q13724 (MOGS_HUMAN)

Synonyms / alternative names: - CDG-IIb / CDG type IIb - Glucosidase I deficiency; GCS1-CDG - Mannosyl-oligosaccharide glucosidase deficiency - Congenital disorder of glycosylation type 2b

Data source type: Individual patients / small international case series (EHR- and research-derived), not population registry aggregates, reflecting the disorder's rarity.

2. Etiology

Primary cause (genetic). Biallelic (homozygous or compound heterozygous) pathogenic variants in MOGS (chromosome 2p13.1) causing near-complete loss of glucosidase I enzymatic activity. This is a monogenic Mendelian defect; there are no established environmental or infectious causes.

• De Praeter (2000, 10788335): first patient was a compound heterozygote for missense variants R486T and F652L; residual enzyme activity <3% of controls; both parents ~50% (obligate carriers) → autosomal recessive.
• Völker (2002, 12145188): glucosidase I activity <1% of control in patient fibroblasts with intermediate parental values.

Genetic risk factors. The only risk factor is inheritance of two pathogenic MOGS alleles. Consanguinity raises risk of homozygous forms; reported cases are from diverse populations (European, Chinese, Japanese, Korean, Indian), consistent with private/family-specific variants rather than a common founder allele.

Environmental risk factors. None identified — disease is fully determined by genotype (congenital, present at birth).

Protective factors. No genetic or environmental protective factors are established. Notably, the glycosylation defect confers an in vitro protective phenotype against certain N-glycosylation–dependent enveloped viruses (see Mechanism/Immune), but this is not a clinically established protective factor.

Gene–environment interactions. Not applicable in a classical sense; disease expression is genotype-driven. Phenotypic variability among patients with similar genotypes suggests modifier effects (genetic background, residual enzyme activity), but specific modifiers are unidentified.

3. Phenotypes

MOGS-CDG is a multisystem disorder with prominent neurological involvement. Frequencies below are qualitative given the small cohort (~30 patients; Teutonico 2024, 38498292; Post 2023, 36651519; Shimada 2022, 35790351).

Severity/progression. Variable, ranging from fatal in infancy (first patient died at 74 days, 10788335) to survival into adulthood (oldest reported 19 years, 33058492). Neurological course is generally progressive (worsening encephalopathy, brain atrophy) with drug-resistant epilepsy.

Quality-of-life impact. Profound: severe neurodevelopmental disability, drug-resistant seizures, feeding/respiratory support needs, and dependence for daily activities. No validated disease-specific QoL instruments exist for this ultra-rare disorder.

4. Genetic / Molecular Information

• Causal gene: MOGS (mannosyl-oligosaccharide glucosidase; a.k.a. glucosidase I, GCS1). HGNC:24862; NCBI Gene 7841; OMIM 601336; UniProt Q13724; Ensembl ENSG00000115275. Reference transcript NM_006302. Located 2p13.1; a compact gene (chr2:74,461,057–74,465,410, GRCh38, ~4.35 kb) encoding an 837-aa, ~91.9 kDa type II single-pass ER membrane glycoprotein of glycoside hydrolase family CAZy GH63 (EC 3.2.1.106).

• Population constraint (gnomAD, GRCh38): MOGS is loss-of-function tolerant at the heterozygous level — pLI ≈ 0 (3.9×10⁻¹⁰), observed/expected LoF oe_lof = 0.66 (LOEUF = 0.84), missense Z = 0.97 (oe_mis = 0.93). This means haploinsufficiency is not disease-causing and healthy carriers are expected — exactly the signature of a recessive enzymopathy requiring biallelic loss of function (matches the ~50% carrier enzyme activity in healthy parents; 12145188).

• Pathogenic variant spectrum — predominantly missense, with some frameshift/duplication:

• R486T (c.1587G>C) and F652L — original compound heterozygote (10788335 12145188)
• c.1239_1267dup (p.Asp414Leufs*17), c.544G>A (p.Gly182Arg), c.1698C>A (p.Asp566Glu) in Chinese siblings (30587846)
• Numerous additional private missense/compound-heterozygous variants across ~30 patients (Shimada 2022 35790351; Teutonico 2024 38498292)
• Variant classification (ACMG/AMP): Pathogenic/Likely pathogenic when biallelic with functional confirmation (enzyme assay or urine Glc₃Man). Structural modeling has been used to support pathogenicity (30587846). ClinVar landscape (Iteration 3 query): 647 MOGS records; of ~300 with classifications — 16 Pathogenic, 9 Likely pathogenic, 2 P/LP (≈27 P/LP), 1 Conflicting, 153 VUS, 114 Likely benign. The large VUS fraction highlights the diagnostic importance of orthogonal functional confirmation (urine Glc₃Man, enzyme assay, or yeast CWH41 complementation) to resolve novel variants.
• Variant type distribution (ClinVar): Overwhelmingly single-nucleotide variants (278) with a minority of small deletions (11), duplications (8), copy-number losses (2), and insertions (1) — i.e., predominantly missense and small frameshift alleles; structural variants are rare (so CMA/karyotype/FISH have little diagnostic role).
• Variant types/class: missense (most common), frameshift/duplication, and predicted splice/nonsense in some cases → loss of function.
• Allele frequency: Individually extremely rare/absent in gnomAD (private variants); no common recurrent allele; carrier frequency very low.
• Somatic vs germline: Germline only.

• Functional consequence: Loss of function (near-complete abolition of glucosidase I catalytic activity, <1–3% residual).

• Modifier genes: None confirmed. Compensatory upregulation of endo-α1,2-mannosidase (MANEA) partially bypasses the block (12145188) and may modulate phenotype.

• Epigenetic information: None reported.
• Chromosomal abnormalities: None; point/small variants only.

5. Environmental Information

• Environmental factors: None causally implicated. Disease is congenital and genotype-determined.
• Lifestyle factors: Not applicable (disease presents at/near birth).
• Infectious agents: Not a cause. Of note, patients show reduced susceptibility to certain enveloped viruses in vitro because viral entry glycoproteins depend on host N-glycosylation (24716661).

6. Mechanism / Pathophysiology

Ordered causal chain (initiating lesion → clinical manifestation):

1. Biallelic loss-of-function variants in MOGS → results in near-complete deficiency (<1–3% residual) of ER glucosidase I. (Demonstrated: enzyme assays, 10788335 12145188.)
2. Loss of glucosidase I activity → fails to cleave the distal α1,2-linked glucose from the protein-bound Glc₃Man₉GlcNAc₂ N-glycan precursor, the first committed step of N-glycan trimming in the ER. (Demonstrated.)
3. Blocked trimming → leads to accumulation of non-deglucosylated high-mannose N-glycans (Glc₃Man₇₋₉GlcNAc₂) on nascent glycoproteins and diversion of the precursor through endo-α1,2-mannosidase, releasing the free tetrasaccharide Glc₃Man, which is excreted in urine (diagnostic biomarker). (Demonstrated, 12145188 36651519 35137040.)
4. Impaired N-glycan maturation → disrupts the calnexin/calreticulin glycoprotein quality-control cycle (which depends on monoglucosylated glycans) and downstream complex/sialylated glycan formation on many secreted and membrane glycoproteins. (Partly inferred from glycan-processing biology; abnormal serum/IgG N-glycomes demonstrated, 35137040.)
5. Aberrant glycoprotein processing → branches into multiple organ effects:
6. Neurological branch: abnormal glycosylation of neuronal ion channels, adhesion molecules, and receptors → developmental & epileptic encephalopathy, hypotonia, progressive cerebral atrophy, movement disorder. (Inferred; clinical correlation strong, 33058492 33261925 38498292.)
7. Immune branch: aberrant IgG glycosylation and shortened immunoglobulin half-life → hypogammaglobulinemia; simultaneously, host-glycan–dependent enveloped viruses (HIV, influenza) show impaired entry/replication → paradoxical relative viral resistance despite low Ig. (Demonstrated in vitro, 24716661.)
8. Hepatic branch: abnormal glycoprotein handling → hepatomegaly, elevated transaminases, coagulopathy (glycosylated clotting factors). (Inferred/clinical.)
9. Dysmorphogenesis branch: disrupted glycosylation during development → craniofacial dysmorphism, digital anomalies, edema. (Inferred.)
10. Cumulative multisystem glycoprotein dysfunction → progressive neurodegeneration, feeding/respiratory failure, and (in severe cases) death in infancy; milder residual function permits survival into childhood/adolescence.

Category detail: - Molecular pathways: N-linked glycan biosynthesis/processing (KEGG hsa00510); ER glycoprotein quality control / calnexin cycle (Reactome "Calnexin/calreticulin cycle", R-HSA-901042; "Asparagine N-linked glycosylation" R-HSA-446203). - Cellular processes: ER protein processing, glycoprotein folding/quality control, ER-associated degradation modulation; neuronal excitability dysregulation (epilepsy). - Protein dysfunction: Loss of function of glucosidase I. Protein architecture (UniProt Q13724): an 837-residue, ~91.9 kDa type II single-pass ER membrane glycoside hydrolase of CAZy family GH63 (EC 3.2.1.106), with a short cytoplasmic tail (1–38), transmembrane signal-anchor (39–59), and a large lumenal catalytic domain (60–837; residues 76–137 required for ER targeting). Catalysis uses a proton donor at position 583 and proton acceptor at 807; the enzyme is itself N-glycosylated at Asn657. Pathogenic missense residues (e.g., R486, F652; 10788335) map to this lumenal catalytic domain near the active-site machinery, disrupting acid–base catalysis and yielding <1–3% residual activity — loss of function by catalytic-domain disruption rather than aggregation. - Metabolic changes: Accumulation and urinary excretion of free oligosaccharide Glc₃Man; hypermannosylated glycopeptides; dyslipidemia and elevated CK reported (36158009). - Immune involvement: Hypogammaglobulinemia (shortened IgG half-life), reduced T/NK proportions, complement C3/C4 deficiency, elevated IL-6, yet reduced enveloped-virus susceptibility (24716661 36158009). - Biochemical abnormality: Enzyme deficiency of glucosidase I (EC 3.2.1.106; CAZy GH63). Catalytic reaction (UniProt Q13724): hydrolysis of the distal α-1,2-glucose from protein-bound Glc3Man9GlcNAc2, releasing β-D-glucose — Reactome R-HSA-4793954 ("Glucosidase I removes glucose from N-glycan"). - Molecular profiling: Serum/IgG N-glycomics show non-deglucosylated Glc₃Man₇₋₉GlcNAc₂ glycans and reduced core-fucosylated complex IgG glycans (35137040); glycomics show compensatory increase in Man₅GlcNAc₂ (36158009).

Suggested ontology terms: GO:0006487 (protein N-linked glycosylation), GO:0009311/GO:0006491 (oligosaccharide/N-glycan processing), GO:0004573 (mannosyl-oligosaccharide glucosidase activity), GO:0005788 (ER lumen). Cell types: CL:0000540 (neuron), CL:0000182 (hepatocyte), CL:0000786 (plasma cell). CHEBI: CHEBI:59080-class oligosaccharides; glucose (CHEBI:17234).

7. Anatomical Structures Affected

• Organ level (primary): Brain/CNS (UBERON:0000955), liver (UBERON:0002107). Secondary: immune system (UBERON:0002405), skeletal muscle/neuromuscular (hypotonia), heart (pericardial effusion – 36158009), kidney (nephromegaly), larynx (laryngomalacia/subglottic stenosis).
• Body systems: Nervous, hepatic/digestive, immune, respiratory, musculoskeletal.
• Tissue/cell level: Neurons and neural tissue (progressive cortical/subcortical atrophy); hepatocytes; plasma cells/B lymphocytes (Ig production); broadly any secretory/membrane-glycoprotein–producing cell.
• Subcellular level: Endoplasmic reticulum (UBERON n/a; GO:0005783 / GO:0005788 ER lumen) — site of glucosidase I action; secretory pathway broadly affected.
• Localization / lateralization: Bilateral, symmetric CNS involvement (diffuse cerebral atrophy). Systemic/generalized rather than focal.

8. Temporal Development

• Onset: Congenital / neonatal — hypotonia, dysmorphism, feeding and respiratory problems from birth; seizures in early infancy.
• Onset pattern: Subacute-to-chronic with early neonatal symptoms and progressive deterioration.
• Progression: Generally progressive neurodegeneration (worsening encephalopathy, cortical/subcortical atrophy). Some manifestations evolve (epileptic spasms in infancy ceasing by ~age 7 while tonic seizures persist; emergence of dystonia/hyperkinetic movement disorder — 33058492).
• Course/duration: Chronic, lifelong. Severe forms are lethal in infancy (74 days in index case); milder forms survive to adolescence/adulthood.
• Remission: No spontaneous remission; seizures are typically drug-resistant. Certain seizure types may abate with age.
• Critical period: Neonatal/early-infancy window is critical for diagnosis and supportive intervention.

9. Inheritance and Population

• Epidemiology: Ultra-rare; ~30 patients reported worldwide as of 2024 (38498292). Prevalence/incidence not formally estimated (Orphanet: <1/1,000,000); no reliable per-100,000 figures.
• Inheritance: Autosomal recessive (both parents obligate carriers with ~50% enzyme activity; 10788335 12145188).
• Penetrance: Complete for biallelic loss-of-function genotypes.
• Expressivity: Variable (lethal infancy → survival to adulthood), even within families.
• Genetic anticipation: Not applicable (not a repeat-expansion disorder).
• Germline mosaicism / founder effects: None documented; variants are private/family-specific.
• Consanguinity: Contributes to homozygous cases in consanguineous families.
• Carrier frequency: Very low (private variants; largely absent from gnomAD). Consistent with this, gnomAD shows MOGS is LoF-tolerant (pLI ≈ 0, LOEUF = 0.84), so heterozygous carriers are asymptomatic and population-frequent enough to be observed, but biallelic combinations are exceedingly rare.
• Population demographics: Reported across European, Chinese, Japanese, Korean, and Indian families; no ethnic predilection or geographic clustering. No clear sex bias (both sexes affected). Age distribution: presents in neonates/infants.

10. Diagnostics

• First-line clue: Multisystem neonatal presentation (hypotonia, seizures, dysmorphism, hepatomegaly) with normal serum transferrin isoelectric focusing — MOGS-CDG escapes routine CDG transferrin screening (33261925).
• Key biochemical test: Urine oligosaccharide analysis (MALDI-TOF MS) detecting the pathognomonic free tetrasaccharide Glc₃Man — reliable screening/confirmation (36651519 35790351 33261925). Quantitative Glc₃Man assays now available.
• Enzyme assay: Glucosidase I activity in fibroblasts/liver markedly reduced (<1–3%) — historical gold standard (10788335 12145188).
• Glycomics: Serum/IgG N-glycan profiling shows accumulated Glc₃Man₇₋₉GlcNAc₂ and altered IgG glycans (35137040 36158009).
• Genetic testing (definitive): Whole-exome sequencing is the principal diagnostic route in most recent cases (38498292 33261925); WGS, targeted CDG gene panels, or single-gene MOGS sequencing also applicable. CMA/karyotype/FISH/mtDNA/repeat testing not indicated. Confirm biallelic MOGS variants + segregation.
• Imaging: Brain MRI — cerebral/cortical–subcortical atrophy, thin corpus callosum, ventricular dilation.
• Supportive labs: Low immunoglobulins/hypogammaglobulinemia, elevated transaminases, coagulopathy, dyslipidemia, elevated CK, complement C3/C4 deficiency (36158009).
• Differential diagnosis: Other CDG type II subtypes, other early-infantile epileptic/developmental encephalopathies, other inborn errors with hypotonia + hepatopathy + dysmorphism; distinguished by normal transferrin IEF + urine Glc₃Man + MOGS genotype. UGGT1-CDG (40267907) is a related ER quality-control CDG in the differential.
• Screening: Not on standard newborn screening panels; cascade carrier testing feasible once a familial variant is known; prenatal/PGT possible for known familial variants.

11. Outcome / Prognosis

• Survival/mortality: Highly variable and often poor. Index patient died at 74 days (10788335); severe neonatal forms with hypoventilation/failure to thrive carry high infant mortality. Milder cases survive into childhood/adolescence; oldest reported 19 years (33058492). No formal 5-/10-year survival statistics exist.
• Morbidity/function: Severe neurodevelopmental disability, drug-resistant epilepsy, hypotonia, feeding and respiratory dependence, movement disorder in survivors — profound long-term disability.
• Complications: Recurrent infections despite paradoxical viral resistance, aspiration/respiratory failure, hepatic dysfunction/coagulopathy, status epilepticus, failure to thrive.
• Recovery potential: No cure; management is supportive. Neurological damage is largely irreversible/progressive.
• Prognostic factors: Degree of residual enzyme activity, severity of neonatal respiratory/feeding compromise, seizure control. No validated molecular prognostic biomarkers; urinary Glc₃Man is diagnostic rather than prognostic.

12. Treatment

No disease-specific or curative therapy exists. Management is multidisciplinary and supportive.

• Pharmacotherapy: Anti-seizure medications for epilepsy (often drug-resistant; combinations frequently required) — NCIT anticonvulsant agents (NCIT:C264). Immunoglobulin replacement (IVIG) for symptomatic hypogammaglobulinemia (NCIT:C29099). Nutritional support, management of reflux/hepatic/coagulation issues.
• Advanced/experimental therapeutics: No approved gene, cell, RNA, or enzyme-replacement therapy. The α-glucosidase inhibitor miglustat (an iminosugar) has been studied in relation to the MOGS glycosylation phenotype and antiviral glycan modification, but not as a disease-modifying treatment for MOGS-CDG itself (33245474). Miglustat NCIT:C61765. A ClinicalTrials.gov API query (Iteration 3) for "MOGS-CDG / glucosidase I deficiency / CDG-IIb" returned no interventional trials specific to MOGS-CDG (keyword hits were unrelated glucosidase disorders — Pompe/Gaucher ERT and gene-therapy studies), confirming the absence of a disease-specific experimental therapeutic pipeline to date.
• Surgical/interventional: Supportive only (e.g., gastrostomy for feeding, respiratory support).
• Supportive/rehabilitative: Physical, occupational, and speech therapy; feeding support; respiratory care; developmental/palliative care.
• Treatment outcomes: Symptomatic benefit only; seizures frequently refractory. No response-rate data given rarity.
• Personalized medicine: Care guided by organ involvement; genetic counseling for families.
• Pharmacogenomics: None established.

13. Prevention

• Primary prevention: Not possible (congenital genetic disorder). Genetic counseling for at-risk families; carrier screening for relatives; prenatal diagnosis and preimplantation genetic testing (PGT) available when the familial MOGS variants are known.
• Secondary prevention: Early recognition via urine oligosaccharide analysis (Glc₃Man) and WES in neonates with encephalopathy/dysmorphism/hepatopathy, enabling timely supportive care.
• Tertiary prevention: Aggressive seizure management, IVIG to reduce infections, nutritional/respiratory support to limit complications.
• Immunization/public health/environmental measures: Not applicable to disease causation; standard immunizations and infection precautions apply, individualized given the immune phenotype.
• Counseling: Autosomal recessive recurrence risk 25% per pregnancy for carrier couples — central genetic counseling message.

14. Other Species / Natural Disease

• Taxonomy / orthologs: MOGS is evolutionarily conserved. Orthologs: mouse Mogs (NCBI Gene 57377), and the yeast homolog CWH41/GLS1 in Saccharomyces cerevisiae (NCBI Taxon 4932). A prokaryotic MOGS (pMOGS) was recently identified in Elizabethkingia meningoseptica (40674822).
• Natural disease in animals: No well-characterized naturally occurring MOGS-CDG equivalent reported in companion animals or wildlife (OMIA has no established entry analogous to human MOGS-CDG). Veterinary relevance limited.
• Comparative biology: The N-glycan trimming pathway and glucosidase I function are highly conserved from yeast to humans, making cross-species functional assays informative (see Model Organisms).
• Transmission: Not applicable (non-infectious, non-zoonotic).

15. Model Organisms

• Yeast (S. cerevisiae): CWH41 (MOGS homolog) knockout strains provide a functional complementation assay — human MOGS and its disease variants can be tested for rescue of the N-glycan profile, allowing pathogenicity assessment of patient mutations (40674822). Strong tool for variant interpretation.
• Prokaryotic MOGS: A bacterial MOGS (pMOGS) characterized as an additional model/reagent for studying MOGS activity (40674822).
• Cellular / in vitro models: Patient-derived skin fibroblasts (enzyme kinetics, glycan analysis; 12145188 10788335); MOGS-null transfected cells used for glycan/antiviral studies (33245474); overexpression systems for glucosidase-inhibitor and viral-glycoprotein studies (24716661 33245474).
• Mammalian genetic models: No widely reported viable Mogs knockout mouse disease model in the retrieved literature; complete loss is expected to be developmentally severe. This is a limitation — no established rodent model recapitulating the human neurological phenotype.
• Model characteristics/limitations: Yeast/cellular systems faithfully recapitulate the biochemical defect (glycan trimming block) and are excellent for variant functional testing, but do not reproduce the multisystem neurological/immunological human phenotype. Applications: variant pathogenicity assays, glycan pathway/compensation studies, and antiviral glycan-modification research.
• Resources: SGD (yeast CWH41), MGI (mouse Mogs), Cellosaurus (patient fibroblast lines).

Key Supported vs. Refuted Hypotheses

Supported: - MOGS-CDG is autosomal recessive, caused by biallelic loss-of-function MOGS variants abolishing glucosidase I activity (10788335 12145188). - The disorder escapes transferrin-based CDG screening; urine Glc₃Man is the diagnostic biomarker (33261925 36651519). - Core phenotype = neonatal hypotonia + developmental/epileptic encephalopathy + dysmorphism + hepatic dysfunction, with a paradoxical immune signature (hypogammaglobulinemia + relative viral resistance) (29235540 24716661).

Refuted / not supported: - Not detectable by standard serum transferrin IEF (normal pattern) — refutes reliance on transferrin screening. - No environmental/infectious cause; not associated with chromosomal abnormalities, somatic mutation, founder alleles, or repeat expansion.

Limitations and Future Directions

• Evidence rests on ~30 individual cases — no registry-scale epidemiology, natural-history, or QoL data; frequencies are qualitative.
• No approved disease-modifying therapy; enzyme/gene/substrate strategies unexplored clinically. Genotype–phenotype correlations and modifiers (e.g., endo-α1,2-mannosidase compensation) merit study.
• A faithful mammalian disease model is lacking; yeast/cellular complementation assays are the current functional standard.
• The therapeutic and antiviral implications of the MOGS glycan phenotype (miglustat, host-glycan–dependent viruses) warrant continued investigation.

Primary References (PMID)

10788335 (De Praeter 2000, first case) · 12145188 (Völker 2002, enzymology/compensation) · 24716661 (Sadat 2014, immune phenotype/viral resistance) · 29235540 (Kim 2018, dysmorphism) · 30587846 (Li 2019, compound het variants) · 33058492 (Lo Barco 2021, oldest patient/movement disorder) · 33245474 (Nunes-Santos 2021, miglustat/glycan) · 33261925 (Anzai 2021, normal transferrin/urine oligosaccharides) · 35137040 (Beimdiek 2022, serum/IgG N-glycomics) · 35790351 (Shimada 2022, clinical/biochemical/genetic characterization) · 36158009 (Abuduxikuer 2022, updated clinical/glycomic) · 36651519 (Post 2023, diagnostic Glc₃Man quantitation) · 38498292 (Teutonico 2024, review, ~30 patients) · 40674822 (Zou 2025, prokaryotic MOGS/yeast complementation) · 41192964 (Shwetabh 2025, DEE case) · 40267907 (Dardas 2025, related UGGT1-CDG).