RARE DISEASERESEARCH ATLAS
Open navigation menu

ORPHA:88639

Neurodegeneration due to 3-hydroxyisobutyryl-CoA hydrolase deficiency

low confidenceDisorder

Also known as: HIBCH deficiency · Methacrylic aciduria · Valine metabolic defect

Query health: suspect — Only one of 2 strategies returned hits (phrase).

Publications

1,035

Trials

0

Interventional, condition-specific

Researchers

1,472

Distinct authors in sample

Gene link

HIBCH

Definitive

Readiness

3/6

Stages with a signal

Clinical definition (Orphanet)

Neurodegeneration due to 3-hydroxyisobutyryl-CoA hydrolase deficiency is characterised by delayed motor development, and neurodegeneration. To date, it has been described in four boys. The syndrome is caused by mutations affecting the two alleles of the HIBCH gene, encoding 3-hydroxyisobutyryl-CoA hydrolase. The mode of transmission has not yet been established.

How rare: <1 / 1 000 000 — fewer than one in a million. In a city the size of Kolkata, that might mean on the order of fifteen people.

Orphanet entry

Cross-references

Joined from Mondo / Orphanet. MeSH labels may enter searches; UMLS / OMIM / NCIT are stored for reference.

Additional Mondo synonyms (3)

3-hydroxyisobutyryl-CoA hydrolase deficiency · methacrylic aciduria · neurodegeneration due to 3-hydroxyisobutyryl-CoA hydrolase deficiency

Research stages

Trial readiness signals

Where this condition sits on an open-data research pipeline — not how close a treatment is, and not medical advice. Empty stages often mean “not in these databases under this Mondo ID,” not “impossible.”

3/6 stages with a signal

No matched interventional trial; the gene is known and literature exists — preclinical or natural-history work may still be the practical next step.

  1. Gene identifiedPresent

    Definitive — HIBCH

  2. LiteraturePresent

    1,035 matched papers (738 in last 10 years) Source

  3. Phenotype characterisedPresent

    55 HPO annotations (e.g. Motor delay; Progressive neurologic deterioration; Epicanthus) Source

  4. Animal modelNot found

    No Alliance genotype “model of” associations via Monarch for these Mondo IDs

  5. Orphan designationNot found

    No FDA or EMA orphan-drug designation matched this disease via UMLS or preferred name Source

  6. Interventional trialNot found

    No matched interventional trial under our ClinicalTrials.gov rules

Biology

Genes and phenotypes

Gene–disease validity from GenCC, plus phenotypes and animal models joined from Monarch Initiative via Mondo ID — not a clinical diagnosis aid.

Do we know what causes it?

Yes — we know a specific gene responsible (HIBCH).

GenCC classification: Definitive.

Phenotypes (Monarch / HPO)

55

Associated phenotypes · MONDO:0009603

  • Motor delay
  • Progressive neurologic deterioration
  • Epicanthus
  • Nystagmus
  • Truncal ataxia

Showing 5 of 55 — open Monarch for the full list.

Animal models (Monarch / Alliance)

None returned for this Mondo ID. Empty here is not proof that no model organism work exists under another name or gene.

Monarch fetch 2026-07-29

Therapies

Designations, candidates, and chemicals

FDA OOPD and EMA orphan designations, Open Targets clinical candidates, and CTD chemical associations via MyDisease.info. These never change the interventional-trial headline.

Orphan designation (FDA · EMA)

No designation matched this disease via UMLS or preferred name on the FDA OOPD mirror or EMA orphan register. Absence here is not proof that none exists under another wording.

Open Targets candidates

No drugs or clinical candidates returned for this Mondo ID on Open Targets.

CTD chemicals (MyDisease.info)

No CTD chemical associations returned for this Mondo ID.

Literature

Is anyone studying this?

1,035

1,035 papers have been published on this condition. That is a real research literature — still far smaller than common diseases (breast cancer: over 700,000 papers). Median papers in the last 10 years for a rare disease in this dataset (publications denominator n=3967) is 59.

1,035 papers since the earliest indexed year in this search — median last-10-year count for a rare disease in this dataset is 59 (publications denominator n=3967).

738 in the last 10 years · low confidence

Phrase hits: 452 · MeSH hits: 0

Open Europe PMC search

Who's working on it?

1,472

Distinct author names in 200 sampled papers — named people below.

Who's working on it?

No interventional trial matched this name; these authors publish on it in the sampled literature — a practical starting point for contact.

  1. 01
    Ferdinandusse S9 papers · 2021

    Laboratory Genetic Metabolic Diseases, Department of Clinical Chemistry, Amsterdam Gastroenterology Endocrinology Metabolism Amsterdam UMC, University of Amsterdam Amsterdam The Netherlands.

    Papers in Europe PMC
  2. 02
    Wang Y8 papers · 2025

    Genetic and Genomic Medicine Division, Department of Pediatrics, UPMC Children's Hospital of Pittsburgh.

    Papers in Europe PMC
  3. 03
    Li X5 papers · 2026

    Department of Neurology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Chongqing, China.

    Papers in Europe PMC
  4. 04
    Liu Z5 papers · 2022

    Department of Pediatric Neurology, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science & and Technology, Wuhan, 430016, China.

    Papers in Europe PMC
  5. 05
    Wanders RJ5 papers · 2016

    Department of Clinical Chemistry and Pediatrics, Emma Children's Hospital, University of Amsterdam, Amsterdam, The Netherlands.

    Papers in Europe PMC
  6. 06
    Yang X5 papers · 2025

    Department of General Practice, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, China.

    Papers in Europe PMC
  7. 07
    Chen Y4 papers · 2025

    Center of Neonatal Disease Screening, Quanzhou Maternity and Children's Hospital, 700 Fengze Street, Quanzhou, Fujian Province, 362000, China.

    Papers in Europe PMC
  8. 08
    Murayama K4 papers · 2021

    Center for Medical Genetics, Department of Metabolism, Chiba Children's Hospital, Chiba, Japan.

    Papers in Europe PMC
  9. 09
    Pitt J4 papers · 2020

    Victorian Clinical Genetics Services, Royal Children's Hospital, Melbourne, Victoria, Australia.

    Papers in Europe PMC
  10. 10
    Wang J4 papers · 2024

    Department of Neurology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.

    Papers in Europe PMC

Clinical research

Is a treatment being tested?

0

interventional trials for this specific condition

No interventional trial testing a treatment matched this specific condition name on ClinicalTrials.gov (observational studies and pan-disease registries are listed separately when present).

Data as of 11 September 2026 · last trial check 11 September 2026

No matched interventional trials. This is true for 77.2% of diseases in the trials denominator (5501 of 7126). Here are the researchers publishing on it.

low confidence · 38.6th percentile (trials denominator)

Recruiting interventional trials

From the matched ClinicalTrials.gov set

No interventional trial testing a treatment was found for this specific condition name on ClinicalTrials.gov.

See who's working on it — people publishing on this disease are often the practical next contact when no trial is listed.

Other registries (secondary)

Broader net from EU CTIS, ISRCTN, and ICTRP when available — deduped against ClinicalTrials.gov IDs already counted above. Dual-model LLM relevance gates what we keep. These rows are not added to the interventional headline.

raw 0 · after dedupe 0 · already on CT.gov 0 · kept 0 · parent 0 · uncertain 0 · dropped 0 · fetched 2026-07-30

Source notes: ictrp: Error: ICTRP public search unavailable (WHO portal is SPA-only; SOAP needs partnership). Tried: https://apps.who.int/tri

No secondary-registry studies passed dual-model relevance for this condition name (after dedupe).

Where to find support

Condition-specific patient organisations, when Orphanet lists them, are on the disease’s Orphanet page. We also link umbrella groups that support undiagnosed and ultra-rare families.

Orphanet entry for Neurodegeneration due to 3-hydroxyisobutyryl-CoA hydrolase deficiency — check Associations / patient organisations on that page.

India — NPRD

Last verified 2026-07-26

Likely covered — the policy lists Organic acidemia as a category (Group 1), and this condition is a form of it. Confirm eligibility with a Centre of Excellence.

Group 1 — one-time curative treatment

Up to ₹50 lakh per patient

Financial support for treatment at notified Centres of Excellence (figures evolved from the original ₹20 lakh Group-1 ceiling).

Policy figures change. Verify current MoHFW / CoE guidance before relying on any amount. Verify

Centres of Excellence (15)
  • All India Institute of Medical Sciences (AIIMS) — New Delhi, Delhi
  • Maulana Azad Medical College — New Delhi, Delhi
  • Sanjay Gandhi Post Graduate Institute of Medical Sciences — Lucknow, Uttar Pradesh
  • Post Graduate Institute of Medical Education and Research (PGIMER) — Chandigarh, Chandigarh
  • Centre for DNA Fingerprinting & Diagnostics with Nizam’s Institute of Medical Sciences — Hyderabad, Telangana
  • King Edward Memorial Hospital — Mumbai, Maharashtra
  • Institute of Post-Graduate Medical Education and Research (IPGMER) — Kolkata, West Bengal
  • Centre for Human Genetics with Indira Gandhi Hospital — Bengaluru, Karnataka
  • Institute of Child Health and Hospital for Children (ICH & HC) — Chennai, Tamil Nadu
  • All India Institute of Medical Sciences (AIIMS) — Jodhpur, Rajasthan
  • Sree Avittam Thirunal Hospital (SAT), Government Medical College — Thiruvananthapuram, Kerala
  • All India Institute of Medical Sciences (AIIMS) — Bhopal, Madhya Pradesh
  • Regional Institute of Medical Sciences (RIMS) — Imphal, Manipur
  • All India Institute of Medical Sciences (AIIMS) — Patna, Bihar
  • Assam Medical College & Hospital — Dibrugarh, Assam

Voluntary contributions / crowdfunding (separate from CoE funding): https://rarediseases.mohfw.gov.in/

Hand-curated for this project. ORPHAcode mappings are best-effort and may be incomplete or imprecise for umbrella categories. Parent (Mondo) matches mean the policy lists a broader category — confirm eligibility with a Centre of Excellence. Financial entitlements summarised from public policy statements and may change. This is not official government guidance.

How we counted this

Europe PMC query (preferred label + any corrected label + Orphanet and Mondo exact synonyms, stoplisted; unioned with resolved MeSH labels when available). UMLS / OMIM / NCIT cross-references are stored on the overview but are not added to the query string.

("Neurodegeneration due to 3-hydroxyisobutyryl-CoA hydrolase deficiency" OR "HIBCH deficiency" OR "Methacrylic aciduria" OR "Valine metabolic defect" OR "3-hydroxyisobutyryl-CoA hydrolase deficiency") OR (MESH:"Beta-Hydroxyisobutyryl CoA Deacylase Deficiency") OR ("HIBCH" OR "HIBCH syndrome" OR "HIBCH-related")

Run this search on Europe PMC

MeSH descriptor terms unioned into the query: Beta-Hydroxyisobutyryl CoA Deacylase Deficiency

ClinicalTrials.gov query (quoted phrases + MeSH via query.cond, plus recall-expansion terms when used):

"Neurodegeneration due to 3-hydroxyisobutyryl-CoA hydrolase deficiency" OR "HIBCH deficiency" OR "Methacrylic aciduria" OR "Valine metabolic defect" OR "3-hydroxyisobutyryl-CoA hydrolase deficiency" OR "Beta-Hydroxyisobutyryl CoA Deacylase Deficiency"

Study-type breakdown: 0 interventional · 0 observational · 0 expanded access. Only interventional studies enter the trial headline.

Query health: suspect — strategies attempted: phrase, mesh; with hits: phrase

Run this search on ClinicalTrials.gov

Confidence reasoning

  • Preferred label is multi-word and distinctive
  • No synonyms dropped by stoplist
  • No label/synonym collisions with other diseases in this corpus
  • Publication count (1035) is implausibly high for prevalence class "<1 / 1 000 000" — treat as possible over-matching, not a measure of research intensity

Ingested 2026-07-27T03:24:12.710Z