ORPHA:79242
Holocarboxylase synthetase deficiency
Also known as: Early-onset multiple carboxylase deficiency · Neonatal multiple carboxylase deficiency
Publications
311
76.5th percentile
Trials
0
Interventional, condition-specific
Researchers
1,267
Distinct authors in sample
Gene link
HLCS
Definitive
Readiness
2/6
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.”
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 — HLCS
- LiteraturePresent
311 matched papers (176 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 (HLCS).
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?
311
311 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.
311 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).
176 in the last 10 years · high confidence · 76.5th percentile (publications denominator)
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 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.
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.
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 2026-07-26Likely 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"
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" OR "HLCS"
Recall-expansion terms: HLCS
Study-type breakdown: 0 interventional · 2 observational · 0 expanded access. Only interventional studies enter the trial headline.
Query health: ok — strategies attempted: phrase, mesh, recall-expansion; 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
Ingested 2026-07-27T02:07:26.743Z