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isobutyryl-CoA dehydrogenase deficiency - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

isobutyryl-CoA dehydrogenase deficiency

MONDO:0012648

Also known as:isobutyric aciduriaAcad8 deficiencyIBD deficiency

Overview

An inborn error of valine metabolism. The prevalence is unknown. Only one symptomatic patient (with anemia, failure to thrive, dilated cardiomyopathy and plasma carnitine deficiency) has been described so far, but several series of patients have been identified through newborn screening programs relying on detection of increased C(4)-carnitine levels by tandem mass spectrometry. The disorder is caused by mutations in the ACAD8 gene (11q25).

GeneticsAutosomal recessive · ACAD8 (chr 11)

ResearchLimited published research (8 articles)

Clinical Presentation

Built from Human Phenotype Ontology (HPO) phenotype annotations and GeneReviews clinical descriptions. Features represent findings documented across known cases — not an exhaustive list of possible symptoms.

Features include: Decreased circulating carnitine concentration, Low red blood cell count (anemia), Low muscle tone (hypotonia), and Enlarged and weakened heart (dilated cardiomyopathy).

Organ System	Phenotype Count	Example Features
Blood and immune system	1	Low red blood cell count (anemia)

Genetic Landscape

Assembled from HGNC gene records, ClinGen gene-disease validity evidence, and ClinVar pathogenic variant data. Validity classifications reflect the strength of published evidence linking each gene to this disease.

ACAD8 encodes acyl-CoA dehydrogenase family member 8 (415 aa). Isobutyryl-CoA dehydrogenase which catalyzes the conversion of 2-methylpropanoyl-CoA to (2E)-2-methylpropenoyl-CoA in the valine catabolic pathway. Highest expression in Thyroid (53.1 TPM) and Brain Cerebellum (35.4 TPM).

Isobutyryl-CoA dehydrogenase deficiency is caused by mutations in the ACAD8 gene on chromosome 11.

The ACAD8 protein participates in isobutyryl-CoA + FAD = methacrylyl-CoA + FADH2 pathway.

ACAD8 is classified as a druggable target (Enzyme category) with score 0.0.

42 pathogenic variants reported in ACAD8 in ClinVar, including hotspot variants LRG_448p1:p.Ala320Thr (2-star review) and LRG_448p1:p.Gly377Ser (2-star review).

Diagnosis

Genetic testing for ACAD8 is available. Testing is considered confirmatory for diagnosis.

Prognosis

Estimated prevalence: Unknown (Unknown prevalence).

Research Landscape

Sourced from ClinicalTrials.gov and PubMed. Publication types are classified using NLM-curated article metadata; research type breakdowns reflect the nature of published work for this disease.

No clinical trials have been registered for isobutyryl-CoA dehydrogenase deficiency.

8 publications have been identified in PubMed for isobutyryl-CoA dehydrogenase deficiency. Research spans Basic Science / Preclinical (38%), Review / Meta-Analysis (25%), and Epidemiology / Natural History (25%).

Recent Publications

Wang JY (2026). [PMID: 42115600](https://pubmed.ncbi.nlm.nih.gov/42115600/). *Nat Commun*. [Basic Science / Preclinical]
Santacruz Reyes MD (2026). [PMID: 41606743](https://pubmed.ncbi.nlm.nih.gov/41606743/). *Orphanet J Rare Dis*. [Review / Meta-Analysis]
Tao Y (2025). [PMID: 40330009](https://pubmed.ncbi.nlm.nih.gov/40330009/). *Front Genet*. [Case Report / Case Series]
Hong S (2025). [PMID: 40618281](https://pubmed.ncbi.nlm.nih.gov/40618281/). *Hum Mol Genet*. [Basic Science / Preclinical]
Huang S (2025). [PMID: 41440809](https://pubmed.ncbi.nlm.nih.gov/41440809/). *Int J Neonatal Screen*. [Review / Meta-Analysis]

Data assembled from 8 of 12 sources · Last updated Sep 19, 2026, 3:02 PM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

OMIM

Online Mendelian Inheritance in Man

OMIM:611283

Orphanet

European rare disease database

Orphanet:79159

GARD

Genetic and Rare Diseases Info Center

GARD:10223

Questions for Your Care Team

→Should my partner and I meet with a genetic counselor to discuss carrier status and family planning?
→Are there specialists or centers of excellence for this condition in my area?
→Is there a patient registry I should consider joining?

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isobutyryl-CoA dehydrogenase deficiency

Overview

Clinical Presentation

Genetic Landscape

Diagnosis

Prognosis

Research Landscape

Recent Publications

Medical References

External Resources

OMIM

Orphanet

GARD

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

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