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IEMbase 0135: ACAD8-related Isobutyryl-CoA dehydrogenase deficiency

Scope

Field Value
IEMbase ID 135
Nosology 1.2.08.01
Gene ACAD8
External IDs OMIM:611283; ORPHA:79159
Generated mapping MAPPED, high confidence
Candidate DisMech targets Isobutyryl-CoA_Dehydrogenase_Deficiency.yaml
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents this as ACAD8-related isobutyryl-CoA dehydrogenase deficiency, with alternate labels isobutyrylglycinuria and IBD. Treatability is marked unknown.

Characteristic biochemical rows include increased urinary isobutyrylglycine, increased C4 acylcarnitine, and decreased free carnitine in dried blood spot and plasma. Other rows include increased esterified carnitine and decreased fibroblast isobutyryl-CoA dehydrogenase activity. Clinical rows include that most patients appear asymptomatic, episodic vomiting, anemia, and dilated cardiomyopathy. No treatment rows are listed.

DisMech phenotype coverage

Isobutyryl-CoA_Dehydrogenase_Deficiency.yaml is the correct local target. It models ACAD8 deficiency as a rare autosomal recessive valine-catabolism disorder often detected by newborn screening through elevated C4-acylcarnitine, with many individuals remaining asymptomatic and a minority having anemia, developmental delay, hepatic abnormalities, vomiting, or rare cardiomyopathy.

The local biochemical section includes C4-acylcarnitine, urinary isobutyrylglycine, free carnitine, C4 ratio biomarkers, and related organic-acid signals. Treatment coverage includes conservative monitoring, dietary management, L-carnitine supplementation when secondary deficiency is present, emergency glucose precautions, and newborn screening.

Concordance and completeness

Judgement: correct mapping with strong local coverage.

IEMbase and DisMech agree on the ACAD8/valine-catabolism mechanism, elevated C4 acylcarnitine, urinary isobutyrylglycine, carnitine depletion, usually asymptomatic course, and rare anemia/cardiomyopathy/vomiting signals. DisMech is substantially richer for mechanism, penetrance nuance, subtype framing, treatment/monitoring, and evidence-backed clinical uncertainty.

Curation actions

  • Keep Isobutyryl-CoA_Dehydrogenase_Deficiency.yaml as the canonical target.
  • No mapping correction is needed.
  • Consider whether decreased fibroblast isobutyryl-CoA dehydrogenase activity or esterified carnitine should be represented explicitly if the local biochemical panel is expanded.