IEMbase 0548: ABCD4-related cblJ methylmalonic aciduria and homocystinuria
Scope
| Field | Value |
|---|---|
| IEMbase ID | 548 |
| Nosology | 21.9.08.01 |
| Gene | ABCD4 |
| External IDs | OMIM:614857; ORPHA:369955 |
| Generated mapping | MAPPED; Inborn_Disorder_of_Cobalamin_Metabolism_and_Transport.yaml#cblJ |
| Candidate DisMech targets | Inborn_Disorder_of_Cobalamin_Metabolism_and_Transport.yaml#cblJ |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents ABCD4-related methylmalonic aciduria and homocystinuria, cblJ type, with alternate labels adenosylcobalamin and methylcobalamin synthesis defect cblJ and cblJ. The record is autosomal recessive, marked treatable, and lists betaine and hydroxocobalamin.
The biochemical rows show combined cobalamin disease: increased urinary and total homocysteine, low-to-normal methionine, increased C3 propionylcarnitine, 3-hydroxypropionic acid, methylcitric acid, and methylmalonic acid, plus low plasma and CSF S-adenosylmethionine. Characteristic clinical rows include megaloblastic anemia, failure to thrive, life-threatening illness, neurologic dysfunction, and impaired vision. Additional rows include cardiomyopathy, cerebral atrophy, dementia, developmental delay, extrapyramidal signs, feeding difficulties, hematuria, hemolytic uremic syndrome, hypotonia, liver dysfunction, maculopathy, myelopathy, hypersegmented neutrophils, nystagmus, psychiatric disturbances, retinopathy, and seizures.
DisMech phenotype coverage
The generated cblJ subtype mapping is correct. The local cobalamin umbrella explicitly includes cblJ as ABCD4 deficiency, with impaired lysosomal cobalamin export producing combined methylmalonic acidemia and homocystinuria. It models reduced active cobalamin cofactor supply, impaired methionine synthase and methylmalonyl-CoA mutase branches, homocysteine accumulation, methionine depletion, methylmalonic acid accumulation, neurologic disease, megaloblastic anemia, failure to thrive, seizures, ocular disease, and hydroxocobalamin plus betaine treatment context.
Concordance and completeness
Judgement: correct high-concordance mapping to the cblJ subtype.
IEMbase and DisMech agree on ABCD4 identity, cblJ scope, combined MMA/HC biochemistry, recessive inheritance, neurologic and hematologic presentation, ocular involvement, and hydroxocobalamin/betaine therapy. DisMech is stronger for the mechanism from cobalamin transport to the two cofactor-dependent enzyme branches.
IEMbase adds useful detail for S-adenosylmethionine in plasma and CSF, hypersegmented neutrophils, maculopathy/retinopathy/nystagmus, myelopathy, hematuria, hemolytic uremic syndrome, and age-patterned severity.
Curation actions
- Keep this record mapped to
Inborn_Disorder_of_Cobalamin_Metabolism_and_Transport.yaml#cblJ. - Consider adding the IEMbase SAM, CSF SAM, hypersegmented-neutrophil, HUS, renal, myelopathy, and detailed ocular rows as enrichment prompts.
- Preserve treatment wording for hydroxocobalamin and betaine.