IEMbase 0066: HIBCH-related 3-hydroxyisobutyryl-CoA hydrolase deficiency
Scope
| Field | Value |
|---|---|
| IEMbase ID | 66 |
| Nosology | 1.2.14.01 |
| Gene | HIBCH |
| External IDs | OMIM:250620 |
| Generated mapping | MAPPED by alias_exact:3 hydroxyisobutyryl coa hydrolase deficiency |
| Candidate DisMech targets | 3-Hydroxyisobutyryl-CoA_Hydrolase_Deficiency.yaml |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents this as autosomal recessive HIBCH-related 3-hydroxyisobutyryl-CoA hydrolase deficiency, with alternate labels beta-hydroxyisobutyryl-CoA deacylase deficiency and 3-hydroxyisobutyric aciduria. Treatability is marked unknown.
The biochemical signal includes high C4-OH 3-hydroxyisobutyrylcarnitine in dried blood spot or plasma, low fibroblast 3-hydroxyisobutyryl-CoA deacylase activity, high urinary 2-hydroxyisovaleric acid, possible anion-gap abnormality, and increased urinary S-2-carboxypropyl-cysteamine and S-2-carboxypropyl-cysteine.
The characteristic clinical signal is developmental delay. Additional features include globus pallidus MRI abnormalities, midbrain abnormalities, cingulate or corpus-callosum agenesis, bilateral toe syndactyly, dysmorphism, dystonia, infection-triggered acute encephalopathy, feeding difficulty, axial hypotonia, intellectual disability, metabolic acidosis, regression, strabismus, and truncal ataxia. The treatment row is valine restriction.
DisMech phenotype coverage
The generated mapping to
3-Hydroxyisobutyryl-CoA_Hydrolase_Deficiency.yaml is correct. DisMech models
HIBCH deficiency as an autosomal recessive valine-catabolism disorder causing
neurodevelopmental impairment and Leigh-like metabolic encephalopathy.
DisMech covers HIBCH enzyme deficiency, valine catabolic block, C4-OH acylcarnitine, urinary 2,3-dihydroxy-2-methylbutyrate, urinary S-(2-carboxypropyl)cysteamine, multiple mitochondrial dysfunction, Leigh-like neurodegeneration, basal ganglia lesions, developmental delay and regression, hypotonia, encephalopathy, feeding difficulty, vomiting, seizures, movement disorder, spasticity, dystonia, microcephaly, visual impairment, cognitive impairment, cerebellar atrophy, blood lactate, biochemical screening, molecular testing, brain MRI, valine-restricted diet, supportive metabolic management, and avoidance guidance.
Concordance and completeness
Judgement: correct mapping and high concordance.
IEMbase adds a few granular details not emphasized in the DisMech entry: fibroblast deacylase activity, urinary 2-hydroxyisovaleric acid, urinary S-2-carboxypropyl-cysteine, midbrain findings, cingulate/corpus-callosum agenesis, toe syndactyly, dysmorphism, strabismus, truncal ataxia, and metabolic acidosis. DisMech is stronger for Leigh-like mechanism, mitochondrial secondary effects, subtype/onset framing, diagnostic context, and valine restriction rationale.
Curation actions
- Keep the generated mapping to
3-Hydroxyisobutyryl-CoA_Hydrolase_Deficiency.yaml. - Consider IEMbase's fibroblast enzyme assay and S-2-carboxypropyl-cysteine row as future diagnostic-marker enrichments.
- Preserve distinction from adjacent valine/isoleucine disorders such as ECHS1 deficiency and ACADSB/SBCADD.