| Disease / synonym field | Summary |
|---|---|
| Preferred disease name | 3-hydroxyisobutyryl-CoA hydrolase deficiency |
| Common synonyms | HIBCH deficiency; HIBCHD; 3-hydroxy-isobutyryl-CoA hydrolase deficiency; Leigh/Leigh-like syndrome due to HIBCH deficiency (pqac-00000000, pqac-00000001, pqac-00000004) |
| OMIM disease ID | OMIM #250620 (reported across cohort/case-series literature) (pqac-00000000, pqac-00000001, pqac-00000005, pqac-00000006) |
| Causal gene | **HIBCH**; gene OMIM reported as **610690** in the Bahrain cohort (pqac-00000001) |
| Inheritance | Autosomal recessive; biallelic pathogenic variants confirmed in reported families and cohorts (pqac-00000000, pqac-00000003, pqac-00000005, pqac-00000006) |
| Core biochemical pathway | Mitochondrial **valine catabolism**; HIBCH catalyzes the conversion of 3-hydroxyisobutyryl-CoA to 3-hydroxyisobutyric acid / the fifth step of valine catabolism (pqac-00000004, pqac-00000008) |
| Pathophysiologic consequence | Accumulation of 3-hydroxyisobutyryl-CoA and reactive valine-derived intermediates (including methacrylyl-CoA-related species), contributing to secondary pyruvate dehydrogenase and respiratory-chain dysfunction / Leigh-like disease (pqac-00000001, pqac-00000017) |
| Key blood biomarker | Elevated **hydroxy-C4 / C4-OH acylcarnitine** (3-hydroxyisobutyryl-carnitine signal); detectable in dried blood spots and sometimes plasma, but can be normal in milder cases (pqac-00000000, pqac-00000004, pqac-00000005, pqac-00000018) |
| Key urine biomarkers | **2,3-dihydroxy-2-methylbutyrate**; **S-(2-carboxypropyl)cysteine (SCPC)**; **S-(2-carboxypropyl)cysteamine (SCPCM)**; some reports also note valine-pathway organic acids and variable 3-hydroxy-isovaleric acid elevations (pqac-00000000, pqac-00000004, pqac-00000007, pqac-00000015) |
| Typical neuroimaging | Bilateral symmetric **basal ganglia** lesions, especially **globus pallidus** T2 hyperintensity; Leigh/Leigh-like pattern; white-matter changes may occur; cavitation/small cysts in pallidum/putamen reported; some long-term follow-up shows **progressive cerebellar atrophy** (pqac-00000001, pqac-00000008, pqac-00000010, pqac-00000012, pqac-00000014) |
| Typical age of onset | Usually **infancy / early childhood**; onset reported from **6 weeks to 6 months** in one cohort, median **13 months** (range 8–18 months) in another; developmental delay/regression commonly begins in the first 2 years of life (pqac-00000002, pqac-00000004) |
| Core clinical picture | Developmental delay or regression, hypotonia, encephalopathy/acute decompensation, feeding difficulties, dystonia/spasticity/ataxia; seizures and ocular abnormalities may occur; phenotype overlaps Leigh syndrome spectrum (pqac-00000001, pqac-00000004, pqac-00000010) |
| Epidemiology / rarity | Ultra-rare. One study citing OMIM reported estimated frequency about **1 in 127,939** in East Asians and **1 in 551,545** in Europeans; earlier work suggested incidence may be around **1 in 130,000** and underdiagnosed (pqac-00000001, pqac-00000004) |
| Newborn screening relevance | Retrospective newborn screening card analysis showed elevated hydroxy-C4 in affected siblings, supporting potential detectability by NBS if hydroxy-C4 is assessed (pqac-00000000, pqac-00000017, pqac-00000018) |
| Diagnostic approach | Parallel **biochemical screening** (acylcarnitine + urinary organic acids) plus **NGS/WES** is recommended; enzymatic confirmation in fibroblasts/tissues is possible but less routinely available (pqac-00000000, pqac-00000004, pqac-00000015, pqac-00000018) |
| Best recent cohort / case-series references | **Al jishi et al., 2024** retrospective Bahrain cohort, 8 patients, DOI/URL: https://doi.org/10.24911/jbcgenetics.183-1722167696 (pqac-00000001, pqac-00000002) |
|  | **Baldo et al., 2024** Leigh syndrome spectrum diagnostic framework; emphasizes parallel biochemical testing and notes HIBCH as a treatable valine-metabolism cause, URL: https://doi.org/10.3390/diagnostics14192133 (pqac-00000015, pqac-00000016) |
|  | **Wang et al., 2021** clinical/metabolic/genetic follow-up of 8 HIBCH patients, URL: https://doi.org/10.3389/fphar.2021.605803 (pqac-00000004) |
|  | **Marti-Sanchez et al., 2021** neurological phenotype/natural history across HIBCH and ECHS1 defects; survival and imaging comparisons, URL: https://doi.org/10.1002/jimd.12288 (pqac-00000008, pqac-00000009, pqac-00000010) |
|  | **Taura et al., 2023** case report expanding imaging spectrum to progressive cerebellar atrophy, URL: https://doi.org/10.1038/s41439-023-00251-y (pqac-00000012, pqac-00000013, pqac-00000014) |
|  | **Stiles et al., 2015** seminal diagnostic/NBS paper on two siblings, URL: https://doi.org/10.1016/j.ymgme.2015.05.008 (pqac-00000000, pqac-00000017, pqac-00000018) |


*Table: This table summarizes the main identifiers, pathway context, biomarkers, imaging features, onset pattern, and key references for 3-hydroxyisobutyryl-CoA hydrolase deficiency. It is designed as a compact evidence-backed reference for a disease knowledge base entry.*