IEMbase 0235: ACADS-related Short-chain acyl CoA dehydrogenase deficiency
Scope
| Field | Value |
|---|---|
| IEMbase ID | 235 |
| Nosology | 4.2.01.01 |
| Gene | ACADS |
| External IDs | OMIM:201470; ORPHA:26792 |
| Generated mapping | MAPPED; Idiopathic_Spontaneous_Coronary_Artery_Dissection.yaml |
| Candidate DisMech targets | SCAD_Deficiency.yaml; generated false target Idiopathic_Spontaneous_Coronary_Artery_Dissection.yaml |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents this as ACADS-related short-chain acyl-CoA dehydrogenase deficiency, with alternate labels ethylmalonic aciduria and SCAD. The record is autosomal recessive and treatability is marked unknown.
The biochemical rows include urinary butyrylglycine, blood/plasma/dried-blood spot C4 butyrylcarnitine, reduced short-chain acyl-CoA dehydrogenase enzyme activity in fibroblasts, ethylmalonic acid, methylsuccinic acid, and low-normal glucose in early life. Clinical rows include behavioral disorder, exercise intolerance, hypoglycemia, predisposition to symptomatic disease, secondary mitochondrial dysfunction, short nose, and small mouth. Characteristic rows include developmental delay, dysmorphic features, epilepsy, failure to thrive, and hypotonia.
DisMech phenotype coverage
SCAD_Deficiency.yaml is the correct target. The local entry covers biallelic
ACADS disease, reduced SCAD activity, impaired short-chain fatty-acid
beta-oxidation, accumulation of butyrylcarnitine/C4, ethylmalonic acid,
methylsuccinic acid, and butyrylglycine, and the current interpretive caution
that SCAD deficiency is often a biochemical phenotype with debated clinical
significance. It also explicitly distinguishes SCAD deficiency from MCAD and
long-chain fatty-acid oxidation disorders by noting that classic hypoketotic
hypoglycemia, recurrent rhabdomyolysis, and cardiomyopathy are generally absent.
The generated target, Idiopathic_Spontaneous_Coronary_Artery_Dissection.yaml,
is unrelated cardiovascular SCAD. It matched through the shared SCAD acronym,
not through disease biology.
Concordance and completeness
Judgement: generated mapping is a false positive; correct local target is
SCAD_Deficiency.yaml.
IEMbase and DisMech agree strongly on ACADS/SCAD identity and the core biochemical diagnostic markers. The main interpretive difference is clinical weighting: IEMbase lists several reported symptomatic features, while DisMech emphasizes that pathogenicity and clinical significance are debated and that many newborn-screening individuals remain asymptomatic. This difference should be preserved as curation nuance rather than treated as disagreement.
Curation actions
- Replace the generated coronary-artery-dissection mapping with
SCAD_Deficiency.yaml. - Keep the SCAD acronym collision as a regression-test case for acronym-only exact-alias matching.
- Use IEMbase as a compact checklist for the C4, ethylmalonic acid, methylsuccinic acid, butyrylglycine, and enzyme-activity markers.