IEMbase 0327: ALG2-related mannosyltransferase 2 deficiency
Scope
| Field | Value |
|---|---|
| IEMbase ID | 327 |
| Nosology | 18.1.08.01 |
| Gene | ALG2 |
| External IDs | OMIM:607906; ORPHA:79326 |
| Generated mapping | CANDIDATE to ALG12_Congenital_Disorder_of_Glycosylation.yaml |
| Candidate DisMech targets | No valid local ALG2-CDG target; Congenital_Myasthenic_Syndrome.yaml is partial secondary context |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents ALG2-CDG/CDG-Ii. Characteristic rows include abnormal jitter, cataract, coloboma, delayed motor development, demyelination, and epilepsy. Additional clinical rows include bulbar dysfunction, congenital myasthenic syndrome, mild facial weakness, hyperreflexia, and hypotonia.
The biochemical signal is a type I glycosylation pattern plus early LLO intermediates: normal-to-increased creatine kinase, increased asialotransferrin and disialotransferrin, increased fibroblast lipid-linked Man1GlcNAc2 and Man2GlcNAc2, type 1 sialotransferrin pattern, decreased tetrasialotransferrin, increased thromboplastin time, increased serum dolichol-linked Man1GlcNAc2 and Man2GlcNAc2, and decreased factor XI. No treatment rows are present.
DisMech phenotype coverage
The generated ALG12-CDG candidate is a false positive from shared CDG-I terminology. ALG12-CDG is a different mannosyltransferase disorder and should not be used as canonical ALG2-CDG coverage.
DisMech has partial context in the congenital myasthenic syndrome entry. Its glycosylation-related CMS subtype explicitly names ALG2 among N-linked glycosylation pathway genes that can impair neuromuscular-junction glycoprotein glycosylation, and it captures the limb-girdle CMS/tubular aggregate/elevated CK branch. However, the local CMS file is an umbrella NMJ transmission entry, not a dedicated ALG2-CDG disease, and it lacks the IEMbase-specific ALG2 lipid-linked Man1/Man2 biochemical profile.
Concordance and completeness
Judgement: true ALG2-CDG disease gap, with local CMS as secondary context only.
IEMbase is useful because it ties the neuromuscular-junction phenotype to a broader CDG biochemical signature. The local CMS entry can help interpret the abnormal jitter, bulbar dysfunction, facial weakness, and congenital myasthenic syndrome features, but it does not cover the CDG-Ii entity.
Curation actions
- Add a standalone ALG2-CDG target before treating this record as mapped.
- Link or cross-reference local glycosylation-related CMS context only as a secondary neuromuscular branch, not as the canonical disease mapping.
- Preserve lipid-linked and dolichol-linked Man1GlcNAc2/Man2GlcNAc2, factor XI, thromboplastin time, abnormal jitter, and bulbar/facial weakness as key review prompts.