IEMbase 0326: ALG8-related glucosyltransferase 2 deficiency
Scope
| Field | Value |
|---|---|
| IEMbase ID | 326 |
| Nosology | 18.1.15.01 |
| Gene | ALG8 |
| External IDs | OMIM:608104; ORPHA:79325 |
| Generated mapping | UNMAPPED |
| Candidate DisMech targets | Reject Autosomal_Dominant_Polycystic_Liver_Disease.yaml#ALG8-related ADPLD |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents ALG8-CDG/CDG-Ih as a congenital disorder of glycosylation. Characteristic rows are hypotonia and psychomotor delay. Additional clinical rows include anemia, asymmetric skull, brachydactyly, camptodactyly, cataract, cerebellar hypoplasia, cerebral atrophy on MRI, cholestasis, delayed fontanel closure, clubfoot, coagulopathy, cryptorchidism, early death, generalized edema, excess skin, facial dysmorphism, feeding difficulties, hepatomegaly, hypertelorism, hypothyroidism, inverted nipples, long philtrum, low-set ears, macrocephaly, microcephaly, optic atrophy, osteopenia, protein-losing enteropathy, renal cysts, renal tubulopathy, seizures, short neck, thrombocytopenia, and ventricular septal defect.
The biochemical rows include increased asialotransferrin and disialotransferrin, increased fibroblast lipid-linked Glc1Man9GlcNAc2, type 1 sialotransferrin pattern, decreased tetrasialotransferrin, decreased albumin, antithrombin III, factor XI, and protein C, and increased serum dolichol-linked Glc1Man9GlcNAc2. No treatment rows are present.
DisMech phenotype coverage
The local Autosomal_Dominant_Polycystic_Liver_Disease.yaml candidate is a
gene-collision false positive. It covers heterozygous ALG8 pathogenic variants
as one cause of autosomal dominant polycystic liver disease, with adult cystic
liver, hepatomegaly, abdominal, renal-cyst, and hepatobiliary complications.
That is mechanistically and clinically distinct from recessive ALG8-CDG.
The CDG mechanism module and existing CDG entries provide pathway context, and some local CDG files mention ALG8 in nonimmune hydrops reviews, but there is no standalone ALG8-CDG disease entry.
Concordance and completeness
Judgement: true local disease gap; reject the ADPLD candidate.
The only meaningful overlap with ADPLD is the ALG8 gene and renal/liver vocabulary. IEMbase points instead to a multisystem infantile CDG with type I transferrin abnormalities, Glc1Man9GlcNAc2 accumulation, coagulation and protein-losing signals, neurodevelopmental involvement, dysmorphism, and cardiac/renal findings.
Curation actions
- Add a standalone ALG8-CDG target before treating this record as mapped.
- Do not map ALG8-CDG to ALG8-related ADPLD; inheritance, mechanism, and phenotype are different.
- Preserve Glc1Man9GlcNAc2, protein-losing enteropathy, renal tubulopathy, cholestasis, coagulopathy, and severe infantile multisystem features as review prompts.