ORPHA:79242
Holocarboxylase synthetase deficiency
Also known as: Early-onset multiple carboxylase deficiency · Neonatal multiple carboxylase deficiency
Publications
2,284
Trials
0
Interventional, condition-specific
Researchers
1,267
Distinct authors in sample
Gene link
HLCS
Definitive
Readiness
3/6
Stages with a signal
Clinical definition (Orphanet)
A rare, early-onset and life-threatening, multiple carboxylase deficiency that when left untreated, is characterized by vomiting, tachypnea, irritability, lethargy, exfoliative dermatitis, and that can worsen to coma and death.
How rare: How common this is has not been clearly measured.
Cross-references
Joined from Mondo / Orphanet. MeSH labels may enter searches; UMLS / OMIM / NCIT are stored for reference.
- MONDO:0009666
- MeSH:D028922
- OMIM:253270
- UMLS:C0268581
- NCIT:C98842
Additional Mondo synonyms (4)
early-onset multiple carboxylase deficiency · holocarboxylase synthase deficiency · holocarboxylase synthetase deficiency · neonatal multiple carboxylase 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.
- Gene identifiedPresent
Definitive — HLCS
- LiteraturePresent
2,284 matched papers (1,739 in last 10 years) Source
- Phenotype characterisedPresent
42 HPO annotations (e.g. Global developmental delay; Elevated urinary 3-methylcrotonylglycine level; Feeding difficulties in infancy) Source
- Animal modelNot found
No Alliance genotype “model of” associations via Monarch for these Mondo IDs
- Orphan designationNot found
No FDA or EMA orphan-drug designation matched this disease via UMLS or preferred name Source
- 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 (HLCS).
GenCC classification: Definitive.
Phenotypes (Monarch / HPO)
42
Associated phenotypes · MONDO:0009666
- Global developmental delay
- Elevated urinary 3-methylcrotonylglycine level
- Feeding difficulties in infancy
- Skin rash
- Tachypnea
Showing 5 of 42 — 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?
2,284
2,284 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.
2,284 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).
1,739 in the last 10 years · low confidence
Phrase hits: 311 · MeSH hits: 2
Who's working on it?
1,267
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.
- 01
- 02Christodoulou J4 papers · 2025
Brain and Mitochondrial Research Group, Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Victoria 3052, Australia.
Papers in Europe PMC - 03Ferreira CR4 papers · 2023
National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Papers in Europe PMC - 04Lin Y4 papers · 2025
Neonatal disease screening center, Quanzhou Children's Hospital, 700 Fengze Street, Quanzhou, 362000, Fujian Province, China.
Papers in Europe PMC - 05Lund AM4 papers · 2021
Department of Clinical Genetics, Juliane Marie Centre 4062, Copenhagen University Hospital, Copenhagen, Denmark. alund@rh.regionh.dk
Papers in Europe PMC - 06Suzuki Y4 papers · 2013
Department of Medical Genetics, Tohoku University School of Medicine.
Papers in Europe PMC - 07van Karnebeek CDM4 papers · 2024
Departments of Pediatrics and Human Genetics, Amsterdam University Medical Centers, University of Amsterdam, 1012 WX Amsterdam, The Netherlands.
Papers in Europe PMC - 08Wolf B4 papers · 2022
Department of Research Administration, Henry Ford Hospital, Detroit, Michigan, USA.
Papers in Europe PMC - 09Yang Y4 papers · 2024
Shanghai Health Development Research Center, Shanghai, China.
Papers in Europe PMC - 10Zeng Y4 papers · 2025
Neonatal Disease Screening Center, Changsha Hospital for Maternal and Child Health Care, Changsha, 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. 2 observational studies did — shown below because natural-history and cohort work can be an important step toward a trial.
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.
Observational and natural-history studies
2 observational studies match this condition. These do not test a treatment and are not counted in the interventional-trial headline, but they are genuine research: natural-history work often defines the endpoints needed for a future rare-disease trial, and families may be able to enroll.
None of the matched observational studies is currently listed as recruiting.
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 Holocarboxylase synthetase deficiency — check Associations / patient organisations on that page.
India — NPRD
Last verified 2026-07-26Likely 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.
("Holocarboxylase synthetase deficiency" OR "Early-onset multiple carboxylase deficiency" OR "Neonatal multiple carboxylase deficiency" OR "holocarboxylase synthase deficiency") OR (MESH:"Holocarboxylase Synthetase Deficiency") OR ("HLCS" OR "HLCS syndrome" OR "HLCS-related")MeSH descriptor terms unioned into the query: Holocarboxylase Synthetase Deficiency
ClinicalTrials.gov query (quoted phrases + MeSH via query.cond, plus recall-expansion terms when used):
"Holocarboxylase synthetase deficiency" OR "Early-onset multiple carboxylase deficiency" OR "Neonatal multiple carboxylase deficiency" OR "holocarboxylase synthase deficiency"
Study-type breakdown: 0 interventional · 2 observational · 0 expanded access. Only interventional studies enter the trial headline.
Query health: ok — strategies attempted: phrase, mesh; with hits: phrase, mesh
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 (2284) is extremely high with unknown/missing prevalence — treat as possible over-matching, not proven research intensity
Ingested 2026-07-27T02:07:26.743Z