IEMbase 0069: MMUT-related methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency
Scope
| Field | Value |
|---|---|
| IEMbase ID | 69 |
| Nosology | 1.2.21.01 |
| Gene | MMUT |
| External IDs | OMIM:251000 |
| Generated mapping | MAPPED by alias_exact:mma |
| Candidate DisMech targets | Methylmalonic_Acidemia.yaml |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents this as autosomal recessive MMUT-related methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency, abbreviated MMA. Treatability is marked yes.
The characteristic biochemical signal includes high methylmalonic acid in plasma and urine, high C3 propionylcarnitine in blood or plasma, high C4-DC methylmalonylcarnitine in dried blood spot or urine, high urinary 3-hydroxypropionic acid and methylcitric acid, high glycine in plasma or urine, high urinary lactate, and low fibroblast methylmalonyl-CoA mutase activity. Additional rows include fibroblast 14C-propionate incorporation, ammonia, anion gap, carnitine, glucose, glutamine, ketones, lactate, and MRS N-acetyl-aspartate.
Characteristic clinical rows include ketoacidotic coma, infection-triggered acute encephalopathy, feeding difficulty, axial hypotonia, lethargy during ketoacidotic episodes, progressive renal impairment, psychomotor delay, and reduced glomerular filtration rate. Additional rows include anemia, ataxia, basal ganglia MRI abnormalities and lesions, brain edema, cardiomyopathy, cerebral atrophy, delayed myelination, dystonia, choreoathetosis, extrapyramidal signs, failure to thrive, hepatomegaly, hyperglycemia, hypothermia during crisis, metabolic acidosis, metabolic stroke, neonatal seizures, neutropenia, optic neuropathy, osteopenia, pancreatitis, renal tubulopathy, respiratory insufficiency, seizures, thrombocytopenia, tubulointerstitial nephritis, vomiting, and white-matter MRI changes.
Treatment rows include avoidance of fasting, carnitine, protein-defined diet, sick-day management, antibiotics, hemodialysis, liver and/or kidney transplantation, carglumic acid, peritoneal dialysis, and sodium benzoate.
DisMech phenotype coverage
The generated mapping to Methylmalonic_Acidemia.yaml is correct. DisMech
models methylmalonic acidemia as an autosomal recessive inborn error of
propionate metabolism caused by MMUT deficiency or by adenosylcobalamin
cofactor-handling defects. It has explicit MMUT genetic coverage, including
mut0 and mut- variant classes.
DisMech covers methylmalonyl-CoA mutase deficiency, methylmalonyl-CoA to succinyl-CoA block, methylmalonic acid, propionyl-CoA and 2-methylcitrate accumulation, mitochondrial dysfunction, metabolic decompensation, hyperammonemia, chronic kidney disease, neurological injury including basal ganglia injury, cardiomyopathy, lipodystrophy-like disease, elevated C3, newborn screening, and biomarkers such as FGF21, GDF15, and LCN2.
Treatment coverage includes protein-restricted diet, hydroxocobalamin for responsive genotypes, carnitine supplementation, acute decompensation management, liver or combined liver-kidney transplantation, genetic counseling, and investigational MMUT mRNA therapy.
Concordance and completeness
Judgement: correct mapping and high concordance.
IEMbase is specifically MMUT/mutase deficiency, while DisMech covers isolated MMA as an umbrella with explicit MMUT, MMAA, and MMAB genetic sections. This is appropriate because the local entry models the broader isolated MMA disease spectrum and already contains the MMUT-specific mechanism.
IEMbase adds granular rows for fibroblast mutase activity, 14C-propionate incorporation, C4-DC methylmalonylcarnitine compartments, reduced GFR, tubulointerstitial nephritis, renal tubulopathy, crisis hypothermia, respiratory insufficiency, delayed myelination, and selected blood-count abnormalities. DisMech is stronger for disease mechanism, renal and cardiac pathophysiology, treatment rationale, trial context, and subtype framing.
Curation actions
- Keep the generated mapping to
Methylmalonic_Acidemia.yaml. - No separate MMUT-only file is needed unless future curation policy splits mut0/mut- from other isolated MMA subtypes.
- Consider IEMbase's enzyme-assay and renal-feature rows as future diagnostic and phenotype enrichments.