IEMbase 0056: IVD-related isovaleric acidemia
Scope
| Field | Value |
|---|---|
| IEMbase ID | 56 |
| Nosology | 1.2.07.01 |
| Gene | IVD |
| External IDs | OMIM:243500 |
| Generated mapping | MAPPED by alias_exact:isovaleric acidemia |
| Candidate DisMech targets | Isovaleric_Acidemia.yaml |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents this as autosomal recessive IVD-related isovaleryl-CoA dehydrogenase deficiency, with alternate labels "Isovaleric acidemia" and "IVA". Treatability is marked yes and the listed prevalence range is 1:100,000-9:100,000.
The biochemical signal includes high urinary isovalerylglycine, high blood or plasma C5 acylcarnitine and C5 isovalerylcarnitine, high C5/C2 ratio, high esterified carnitine, low free carnitine, low fibroblast IVD activity, high urinary 3-hydroxyisovaleric acid, high plasma isovaleric acid, and possible hyperammonemia, positive anion gap, low calcium or glucose, and increased lactate or uric acid. The clinical signal emphasizes coma during ketoacidotic episodes, acute encephalopathic crisis, feeding difficulty, lethargy, sweaty-feet odor, and episodic vomiting, with additional cytopenias, seizures, hypotonia, hepatomegaly, hypoglycemia, metabolic acidosis, pancreatitis, globus pallidus abnormalities, and white-matter changes.
IEMbase treatments are avoidance of fasting, carnitine, protein-defined diet, sick-day management, and N-carbamyl-L-glutamate/carglumic acid.
DisMech phenotype coverage
The generated mapping to Isovaleric_Acidemia.yaml is correct. DisMech models
IVA as an autosomal recessive leucine-catabolism disorder caused by IVD
deficiency, with accumulation of isovaleric acid, 3-hydroxyisovaleric acid,
isovalerylcarnitine C5, and isovalerylglycine.
DisMech covers the core severe neonatal crisis phenotype and attenuated newborn-screening phenotype, including ketoacidosis, metabolic acidosis, hyperammonemia, encephalopathy, vomiting, lethargy, seizures, intellectual disability risk, growth impairment, characteristic odor, secondary carnitine depletion, and pancytopenia. It also models secondary hyperammonemia through NAGS inhibition by isovaleryl-CoA and includes leucine/protein restriction, carnitine, glycine, carglumic acid, and acute catabolic-episode management.
Concordance and completeness
Judgement: correct mapping and high concordance.
IEMbase adds useful diagnostic-panel granularity, especially C5/C2 ratio, compartment-specific free and esterified carnitine values, fibroblast enzyme activity, MRS lactate/N-acetylaspartate ratio, calcium, and selected imaging and hematologic features. DisMech is stronger for mechanistic explanation, detoxification through carnitine and glycine conjugation, secondary hyperammonemia, and treatment rationale.
Curation actions
- Keep the generated mapping to
Isovaleric_Acidemia.yaml. - Preserve C5-isomer caution when comparing IVA to ACADSB/SBCADD records; C5 alone is not disease-specific without follow-up testing.
- Consider IEMbase's globus pallidus, white-matter, and ratio-marker details as possible future diagnostic or phenotype enrichments.