ORPHA:35701
3-hydroxy-3-methylglutaryl-CoA synthase deficiency
Also known as: HMG-CoA synthase deficiency
Query health: suspect — Only one of 2 strategies returned hits (phrase).
Publications
73
55.4th percentile
Trials
0
Interventional, condition-specific
Researchers
520
Distinct authors in sample
Gene link
HMGCS2
Definitive
Readiness
2/6
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.
Cross-references
Joined from Mondo / Orphanet. MeSH labels may enter searches; UMLS / OMIM / NCIT are stored for reference.
- MONDO:0011614
- MeSH:C567784
- OMIM:605911
- UMLS:C2751532
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.”
2/6 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.
- Gene identifiedPresent
Definitive — HMGCS2
- LiteraturePresent
73 matched papers (56 in last 10 years) Source
- Phenotype characterisedNot checked
Not yet enriched from Monarch / HPO
- Animal modelNot checked
Not yet enriched from Monarch / Alliance
- Orphan designationNot checked
FDA/EMA orphan-drug designation not enriched yet
- 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)
Not enriched in this build — Monarch phenotype joins were not run for this record.
Animal models (Monarch / Alliance)
Not enriched in this build.
Literature
Is anyone studying this?
73
73 papers have ever been published on this condition (under this name). For scale, breast cancer has over 700,000. Median papers in the last 10 years for a rare disease in this dataset (publications denominator n=5449) is 41.
73 papers since the earliest indexed year in this search — median last-10-year count for a rare disease in this dataset is 41 (publications denominator n=5449).
56 in the last 10 years · high confidence · 55.4th percentile (publications denominator)
Phrase hits: 73 · MeSH hits: 0
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.
- 01Pié 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 - 02Hegardt 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 - 03Zschocke J4 papers · 2015
Division of Metabolic and Endocrine Diseases, University Children's Hospital, Heidelberg, Germany.
Papers in Europe PMC - 04Aledo R3 papers · 2006
Department of Molecular Biology, International University of Catalonia, Barcelona, Spain.
Papers in Europe PMC - 05Casals N3 papers · 2006Papers in Europe PMC
- 06Ferreira CR3 papers · 2023
National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Papers in Europe PMC - 07Gómez-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 - 08Puisac 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 - 09Arnedo 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 - 10Awano 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 27 July 2026
No matched interventional trials. This is true for 73% of diseases in the trials denominator (5114 of 7003). Here are the researchers publishing on it.
high confidence · 36.5th 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.
Where to find support
We do not yet link condition-specific patient organisations. These umbrella groups support undiagnosed and ultra-rare families:
India — NPRD
Last verified 2026-07-26This 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"
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" OR "HMGCS2"
Recall-expansion terms: HMGCS2
Study-type breakdown: 0 interventional · 0 observational · 0 expanded access. Only interventional studies enter the trial headline.
Query health: suspect — strategies attempted: phrase, recall-expansion; 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
Ingested 2026-07-26T23:47:44.240Z