IEMbase 0089: MMADHC-related homocystinuria, cblDv1 type
Scope
| Field | Value |
|---|---|
| IEMbase ID | 89 |
| Nosology | 21.9.11.02 |
| Gene | MMADHC |
| External IDs | OMIM:277410 |
| Generated mapping | UNMAPPED |
| Candidate DisMech targets | Manual target Inborn_Disorder_of_Cobalamin_Metabolism_and_Transport.yaml#cblD |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents this as autosomal recessive MMADHC-related homocystinuria, cblD variant 1 type, with alternate labels cblD-HC and homocystinuria cblD type variant 1. Treatability is marked yes.
The characteristic clinical rows are megaloblastic anemia and neurological symptoms.
The biochemical panel is remethylation-predominant: homocysteine in urine, total plasma homocysteine, low-to-normal plasma methionine, and reduced S-adenosylmethionine in CSF or plasma. Methylmalonic acid in plasma and urine is present but recorded as normal across age strata for this cblD-HC record.
Treatment rows include betaine and hydroxycobalamin.
DisMech phenotype coverage
The generated UNMAPPED status is a false negative. The best local target is
Inborn_Disorder_of_Cobalamin_Metabolism_and_Transport.yaml#cblD.
DisMech already has a cblD subtype for MMADHC deficiency and explicitly states that MMADHC defects can produce isolated methylmalonic acidemia, isolated homocystinuria, or combined disease. The pathophysiology section includes MMADHC in impaired intracellular cobalamin cofactor synthesis and cites cblD-homocystinuria among the intracellular cobalamin processing defects. The remethylation branch captures impaired methionine synthase activity, homocysteine accumulation, methionine depletion, megaloblastic anemia, and hydroxocobalamin/betaine treatment logic.
Concordance and completeness
Judgement: false-negative mapping with high local umbrella-level coverage.
The main gap is subtype granularity. DisMech currently has one cblD subtype rather than separate cblD-HC/cblDv1, cblD-MMA/cblDv2, and combined cblD forms. That loses the IEMbase distinction between remethylation-predominant disease and isolated MMA disease.
Curation actions
- Update the mapping logic or manual crosswalk to resolve this record to
Inborn_Disorder_of_Cobalamin_Metabolism_and_Transport.yaml#cblD. - Consider splitting cblD into cblD-HC, cblD-MMA, and combined forms if subtype granularity becomes important.
- Preserve the remethylation-specific cblD-HC signal: high homocysteine, low-to-normal methionine, megaloblastic anemia, and betaine plus hydroxycobalamin therapy.