IEMbase 0325: ALG12-related mannosyltransferase 8 deficiency
Scope
| Field | Value |
|---|---|
| IEMbase ID | 325 |
| Nosology | 18.1.13.01 |
| Gene | ALG12 |
| External IDs | OMIM:607143; ORPHA:79324 |
| Generated mapping | MAPPED to ALG12_Congenital_Disorder_of_Glycosylation.yaml |
| Candidate DisMech targets | ALG12_Congenital_Disorder_of_Glycosylation.yaml |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents ALG12-CDG/CDG-Ig as a gene-specific congenital disorder of glycosylation. Characteristic rows include impaired hearing, micropenis, psychomotor delay, retinal detachment, and strabismus. Additional clinical rows include agenesis of the corpus callosum, hypertrophic cardiomyopathy, cerebellar hypoplasia, clubfoot, deeply set eyes, dolichocephaly, dwarfism, early death, edema, facial dysmorphism, failure to thrive, feeding difficulties, gastric tube feeding, gastrointestinal dysmotility, hypoglycemia, hypoplastic nails, hypospadias, hypotonia, inverted nipples, male genital hypoplasia, malrotation, maternal HELLP syndrome, microcephaly, midface hypoplasia, prematurity, prominent nose, short metacarpals, skeletal dysplasia, temporal hypoplasia with dilated external CSF spaces, thrombocytopenia, and ventricular septal defect.
The biochemical profile includes normal-to-increased transaminase, increased asialotransferrin and disialotransferrin, increased fibroblast lipid-linked Man7GlcNAc2, type 1 sialotransferrin pattern, decreased tetrasialotransferrin, low-to-normal cholesterol and glucose, decreased antithrombin III, increased dolichol-linked Man7GlcNAc2, low-to-normal IGF BP3 and IGF1, and low-to-normal immunoglobulins. No treatment rows are present.
DisMech phenotype coverage
The generated mapping is correct. DisMech has a dedicated ALG12-CDG entry with the same MONDO identity, ALG12/CDG-Ig synonyms, autosomal recessive ALG12 causation, type I transferrin hypoglycosylation, abnormal oligomannose N-glycans, hypoglycosylated antithrombin and factor XI, and multisystem phenotypes including developmental delay, hypotonia, failure to thrive, short stature, recurrent respiratory infections, facial dysmorphism, decreased immunoglobulins, coagulation abnormality, hypoplastic male genitalia, skeletal dysplasia, multicystic kidney dysplasia, ventricular septal defect, and scoliosis.
DisMech is stronger than IEMbase for mechanism and treatment context because it models ALG12 mannosyltransferase deficiency and includes supportive care and immunoglobulin replacement. IEMbase is broader for individual clinical feature prompts.
Concordance and completeness
Judgement: correct high-concordance mapping.
The two resources agree on the core disease entity, gene, type I CDG biochemistry, neurodevelopmental phenotype, growth and feeding involvement, male genital findings, skeletal/cardiac involvement, coagulation abnormalities, and immune signal. IEMbase adds granular features for review: corpus callosum agenesis, cerebellar hypoplasia, hearing and retinal findings, GI dysmotility, hypoglycemia, endocrine-growth markers, maternal HELLP, prematurity, and detailed dysmorphism.
Curation actions
- Keep the generated ALG12-CDG mapping.
- Consider future enrichment of the local entry with IEMbase-only neurologic imaging, ocular, hearing, GI dysmotility, hypoglycemia, IGF, and prenatal context after source verification.
- Treat absent IEMbase treatment rows as incomplete IEMbase coverage, not as a contradiction of local supportive and immunoglobulin-replacement therapy.