IEMbase 0324: ALG3-related mannosyltransferase 6 deficiency
Scope
| Field | Value |
|---|---|
| IEMbase ID | 324 |
| Nosology | 18.1.11.01 |
| Gene | ALG3 |
| External IDs | OMIM:601110; ORPHA:79321 |
| Generated mapping | CANDIDATE to ALG12_Congenital_Disorder_of_Glycosylation.yaml |
| Candidate DisMech targets | No valid local ALG3-CDG target |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents ALG3-CDG/CDG-Id as an autosomal recessive congenital disorder of glycosylation. Characteristic rows include axial hypotonia, clubfoot, coloboma, epilepsy, facial dysmorphism, extremity hypertonia, hypsarrhythmia on EEG, microcephaly, and psychomotor retardation. Additional clinical rows include arachnodactyly, cerebral atrophy on MRI, congenital heart defects, feeding difficulties, micrognathia, optic atrophy, skeletal dysplasia, and strabismus.
The biochemical profile is type I CDG-like and granular for ALG3: low free fatty acids and ketones during hypoglycemia, increased asialotransferrin and disialotransferrin, increased fibroblast lipid-linked Man5GlcNAc2, type 1 sialotransferrin pattern, decreased tetrasialotransferrin, decreased glucose, decreased antithrombin III, apolipoprotein B, and protein S, and increased insulin during hypoglycemia. No treatment rows are present.
DisMech phenotype coverage
The generated ALG12-CDG candidate is a false positive caused by shared CDG-I terminology and overlapping type I glycosylation phenotypes. The local ALG12 entry is gene-specific to ALG12/CDG-Ig and centers on ALG12 mannosyltransferase activity with Man7-linked oligosaccharide abnormalities. It is not disease coverage for ALG3/CDG-Id.
The CDG grouping and CDG mechanism module provide family context for type I lipid-linked oligosaccharide assembly defects, but there is no standalone ALG3-CDG disease entry. ALG9 and ALG12 files should remain comparator context only.
Concordance and completeness
Judgement: true local disease gap; reject the ALG12 candidate.
IEMbase supplies a useful future-curation seed: early neurologic disease, ocular and skeletal features, congenital heart defects, hypoglycemia-related ketone/free-fatty-acid rows, coagulation/protein abnormalities, and the ALG3-relevant Man5GlcNAc2 lipid-linked oligosaccharide signal.
Curation actions
- Add a standalone ALG3-CDG target before treating this record as mapped.
- Do not map ALG3-CDG to ALG12-CDG or ALG9-CDG solely because they share the type I CDG biochemical class.
- Preserve Man5GlcNAc2, hypoglycemia, antithrombin III, apolipoprotein B, and protein S rows as disease-specific review prompts.