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ORPHA:35701

3-hydroxy-3-methylglutaryl-CoA synthase deficiency

low confidenceDisorder

Also known as: HMG-CoA synthase deficiency

Publications

3,454

Trials

0

Interventional, condition-specific

Researchers

520

Distinct authors in sample

Gene link

HMGCS2

Definitive

Readiness

4/6

Stages with a signal

Clinical definition (Orphanet)

3-hydroxy-3-methylglutaryl-CoA synthase deficiency (HMG-CoA synthase deficiency) is a rare recessively inherited disorder of ketone body metabolism, reported in less than 20 patients to date, characterized clinically by episodes of decompensation (often associated with gastroenteritis or fasting) that present with vomiting, lethargy, , non ketotic and, in rare cases, coma. Patients are mostly asymptomatic between acute episodes. HMG-CoA synthase deficiency requires an early diagnosis in order to avoid hypoglycemic crises that can lead to permanent brain damage or death.

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 (1)

HMG-CoA synthase-2 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.”

4/6 stages with a signal

No matched interventional trial, but a gene association and an animal model are on record — often described as translation-ready / stalled at the clinical step.

  1. Gene identifiedPresent

    Definitive — HMGCS2

  2. LiteraturePresent

    3,454 matched papers (2,664 in last 10 years) Source

  3. Phenotype characterisedPresent

    23 HPO annotations (e.g. Seizure; Abnormality of metabolism/homeostasis; Hypoglycemia) Source

  4. Animal modelPresent

    2 genotype models (Mus musculus) Source

  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 (HMGCS2).

GenCC classification: Definitive.

Phenotypes (Monarch / HPO)

23

Associated phenotypes · MONDO:0011614

  • Seizure
  • Abnormality of metabolism/homeostasis
  • Hypoglycemia
  • Diarrhea
  • Encephalopathy

Showing 5 of 23 — open Monarch for the full list.

Animal models (Monarch / Alliance)

2

Model associations linked to this Mondo ID

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?

3,454

3,454 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.

3,454 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).

2,664 in the last 10 years · low confidence

Phrase hits: 73 · MeSH hits: 0

Open Europe PMC search

Who's working on it?

520

Distinct author names in 73 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
    Pié J6 papers · 2025

    Unit of Clinical Genetics and Functional Genomics, Department of Pharmacology-Physiology, School of Medicine, University of Zaragoza, CIBERER-GCV02 and ISS-Aragon, E-50009 Zaragoza, Spain. juanpie@unizar.es.

    Papers in Europe PMC
  2. 02
    Hegardt FG5 papers · 2013

    Department of Biochemistry and Molecular Biology, School of Pharmacy, University of Barcelona, Av/ Diagonal 643, 08028 Barcelona, Spain. hegardt@farmacia.far.ub.es

    Papers in Europe PMC
  3. 03
    Zschocke J4 papers · 2015

    Division of Metabolic and Endocrine Diseases, University Children's Hospital, Heidelberg, Germany.

    Papers in Europe PMC
  4. 04
    Aledo R3 papers · 2006

    Department of Molecular Biology, International University of Catalonia, Barcelona, Spain.

    Papers in Europe PMC
  5. 05
    Casals N3 papers · 2006
    Papers in Europe PMC
  6. 06
    Ferreira CR3 papers · 2023

    National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.

    Papers in Europe PMC
  7. 07
    Gómez-Puertas P3 papers · 2025

    Molecular Modelling Group, Center of Molecular Biology "Severo Ochoa" (CSIC-UAM), Cantoblanco, E-28049 Madrid, Spain. pagomez@cbm.csic.es.

    Papers in Europe PMC
  8. 08
    Puisac B3 papers · 2025

    Unit of Clinical Genetics and Functional Genomics, Department of Pharmacology-Physiology, School of Medicine, University of Zaragoza, CIBERER-GCV02 and ISS-Aragon, E-50009 Zaragoza, Spain. puisac@unizar.es.

    Papers in Europe PMC
  9. 09
    Arnedo M2 papers · 2025

    Unit of Clinical Genetics and Functional Genomics, Department of Pharmacology and Physiology, School of Medicine, University of Zaragoza, CIBERER and IIS-Aragon, 50009 Zaragoza, Spain.

    Papers in Europe PMC
  10. 10
    Awano H2 papers · 2026

    Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.

    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 2026-07-29

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 3-hydroxy-3-methylglutaryl-CoA synthase deficiency — check Associations / patient organisations on that page.

India — NPRD

Last verified 2026-07-26

This ORPHAcode is not on our curated NPRD list (direct or Mondo-parent match). That does not decide clinical eligibility; families in India should ask a notified Centre of Excellence about current coverage.

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.

("3-hydroxy-3-methylglutaryl-CoA synthase deficiency" OR "HMG-CoA synthase deficiency" OR "HMG-CoA synthase-2 deficiency") OR ("HMGCS2" OR "HMGCS2 syndrome" OR "HMGCS2-related")

Run this search on Europe PMC

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

"3-hydroxy-3-methylglutaryl-CoA synthase deficiency" OR "HMG-CoA synthase deficiency" OR "HMG-CoA synthase-2 deficiency"

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

Query health: ok — strategies attempted: phrase; 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 (3454) is implausibly high for prevalence class "<1 / 1 000 000" — treat as possible over-matching, not a measure of research intensity

Ingested 2026-07-26T23:47:44.240Z