IEMbase 0063: ACADSB-related 2-methylbutyryl-CoA dehydrogenase deficiency
Scope
| Field | Value |
|---|---|
| IEMbase ID | 63 |
| Nosology | 1.2.09.01 |
| Gene | ACADSB |
| External IDs | OMIM:610006 |
| Generated mapping | MAPPED by alias_exact:2 methylbutyryl coa dehydrogenase deficiency |
| Candidate DisMech targets | 2-Methylbutyryl-CoA_Dehydrogenase_Deficiency.yaml |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents this as autosomal recessive ACADSB-related 2-methylbutyryl-CoA dehydrogenase deficiency, with alternate labels short/branched-chain acyl-CoA dehydrogenase deficiency, 2-methylbutyrylglycinuria, and MBCD. Treatability is marked unknown.
The biochemical signal includes high urinary 2-methylbutyrylglycine, normal-high isobutyrylglycine, high blood or plasma C5 2-methylbutyrylcarnitine, high C5/C2 ratio, low fibroblast 2-methylbutyryl-CoA dehydrogenase activity, normal-high 2-ethylhydracrylic acid, high urinary 2-methylbutyric acid, possible anion-gap abnormality, and low-normal glucose.
IEMbase does not list characteristic clinical features. Additional features include autism spectrum disorder, decreased cortical sulci, hypoglycemia, axial hypotonia, asymptomatic individuals, and psychomotor delay. No treatment rows are present in the cached record.
DisMech phenotype coverage
The generated mapping to
2-Methylbutyryl-CoA_Dehydrogenase_Deficiency.yaml is correct. DisMech models
SBCADD as an autosomal recessive isoleucine-metabolism disorder caused by
ACADSB variants, with accumulation of C5 acylcarnitine
2-methylbutyrylcarnitine, urinary 2-methylbutyrylglycine, and
2-ethylhydracrylic acid through R-pathway rerouting.
DisMech covers the largely asymptomatic newborn-screening phenotype, the minority symptomatic phenotype with developmental delay, seizures, hypotonia, failure to thrive, microcephaly, autism, dyskinetic cerebral palsy, and muscle atrophy, plus stress-sensitive decompensation, C5-isomer ambiguity, ACAD substrate promiscuity, carnitine supplementation, catabolic-stress avoidance, emergency protocols, controversial diet management, valproate avoidance, newborn screening, and longitudinal monitoring.
Concordance and completeness
Judgement: correct mapping and high concordance.
IEMbase adds useful compact diagnostic details, especially the C5/C2 ratio, fibroblast enzyme activity, urinary 2-methylbutyric acid, decreased cortical sulci, hypoglycemia, and axial hypotonia. DisMech is stronger for the mechanistic distinction from IVA, the R-pathway/2-ethylhydracrylic acid branch, the mostly asymptomatic course, and management uncertainty.
Curation actions
- Keep the generated mapping to
2-Methylbutyryl-CoA_Dehydrogenase_Deficiency.yaml. - Preserve explicit distinction from IVA because both can produce elevated C5.
- Consider IEMbase C5/C2 and fibroblast enzyme rows as future diagnostic enrichment candidates.