IEMbase 0088: MMADHC-related methylmalonic aciduria, cblDv2 type
Scope
| Field | Value |
|---|---|
| IEMbase ID | 88 |
| Nosology | 21.9.11.01 |
| Gene | MMADHC |
| External IDs | OMIM:277410 |
| Generated mapping | UNMAPPED |
| Candidate DisMech targets | Best fuzzy candidate Inborn_Disorder_of_Cobalamin_Metabolism_and_Transport.yaml |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents this as autosomal recessive MMADHC-related methylmalonic aciduria, vitamin B12-responsive cblD variant 2 type, with alternate labels cblD type and cblD-MMA. Treatability is marked yes.
The characteristic clinical rows include acidosis, dehydration, acute encephalopathic crisis, failure to thrive, ketosis, life-threatening illness, and vomiting.
The biochemical panel includes elevated urinary and plasma methylmalonic acid, urinary methylcitric acid, urinary 3-hydroxypropionic acid, C3 propionylcarnitine in blood or plasma, ammonia, anion gap, lactate, total plasma homocysteine, and free carnitine in dried blood spot or plasma.
Treatment rows include antibiotics, avoidance of fasting, carnitine, hemodialysis, hydroxycobalamin, liver and/or kidney transplantation, carglumic acid, peritoneal dialysis, protein-defined diet, sick-day management, and sodium benzoate.
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, describing MMADHC variants that can produce isolated methylmalonic acidemia, isolated homocystinuria, or combined disease. The pathophysiology section includes MMADHC in impaired intracellular cobalamin cofactor synthesis and cites the variant 2 form of cblD as linked to adenosylcobalamin synthesis. This matches IEMbase's cblDv2/cblD-MMA framing.
Methylmalonic_Acidemia.yaml is relevant for shared isolated-MMA phenotype and
treatment coverage, but it currently lists MMUT, MMAA, and MMAB explicitly and
does not provide an MMADHC/cblD genetic section. The cobalamin umbrella is
therefore the better canonical target for this IEMbase record.
Concordance and completeness
Judgement: false-negative mapping with moderate-to-high local coverage.
The main local gap is subtype granularity: DisMech has a single cblD subtype rather than separate cblD-MMA/cblDv2, cblD-HC/cblDv1, and combined cblD forms. It also does not mirror all IEMbase acute-treatment rows for the isolated MMA presentation.
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-MMA, cblD-HC, and combined forms if subtype granularity becomes important.
- Consider adding MMADHC/cblD-v2 as explicit secondary genetic coverage in
Methylmalonic_Acidemia.yamlif isolated MMA is kept as a broad entry.