ORPHA:300
Bifunctional enzyme deficiency
Query health: suspect — Only one of 2 strategies returned hits (phrase).
Publications
321
72.5th percentile
Trials
2
Interventional, condition-specific
Researchers
1,331
Distinct authors in sample
Gene link
HSD17B4
Definitive
Readiness
3/6
Stages with a signal
Clinical definition (Orphanet)
A rare peroxisomal beta-oxidation disorder characterized by deficiency of peroxisomal D-bifunctional protein, type 1 being caused by deficiency of both dehydrogenase and hydratase activities of the , and types 2 and 3 by hydratase or dehydrogenase deficiency alone, while type 4 is due to compound heterozygous mutations affecting both units and represents a clinically milder . Types 1-3 are typically fatal in infancy. Patients present with early onset of generalized , , severe global , craniofacial dysmorphism (large fontanel, high forehead, hypertelorism, epicanthal folds) and elevated plasma very long chain fatty acids. Variable features include , polymicrogyria, and cerebral white matter abnormalities, among others.
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:0009855
- OMIM:261515
- UMLS:C0342870
- NCIT:C119676
Additional Mondo synonyms (7)
D-bifunctional enzyme deficiency · HSD17B4 deficiency · d-bifunctional protein deficiency · multifunctional enzyme deficiency · peroxisomal multifunctional enzyme (MFE2) deficiency · peroxisomal multifunctional enzyme deficiency · pseudo-Zellweger syndrome
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
An interventional trial matched this condition name on ClinicalTrials.gov — see trials below.
- Gene identifiedPresent
Definitive — HSD17B4
- LiteraturePresent
321 matched papers (140 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 trialPresent
2 matched on ClinicalTrials.gov
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 (HSD17B4).
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?
321
321 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.
321 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).
140 in the last 10 years · medium confidence · 72.5th percentile (publications denominator)
Phrase hits: 321 · MeSH hits: 0
Who's working on it?
1,331
Distinct author names in 200 sampled papers — named people below.
Who's working on it?
People publishing on this condition (sampled Europe PMC records). Affiliation is the most recent found in that sample.
- 01Wanders RJ20 papers · 2015
Dept. of Pediatrics, University Hospital Amsterdam, The Netherlands.
Papers in Europe PMC - 02Ferdinandusse S10 papers · 2022
Laboratory Genetic Metabolic Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. s.ferdinandusse@amc.uva.nl.
Papers in Europe PMC - 03Shimozawa N8 papers · 2021
Division of Genomics Research, Life Science Research Center, Gifu University, Gifu, Japan.
Papers in Europe PMC - 04Suzuki Y8 papers · 2001
Department of Pediatrics, Gifu University School of Medicine.
Papers in Europe PMC - 05Wang Y7 papers · 2025
Department of Molecular & Human Genetics, Baylor College of Medicine, and Baylor Genetics Laboratories, Houston, Texas, USA.
Papers in Europe PMC - 06Waterham HR6 papers · 2020
Laboratory Genetic Metabolic Diseases, Academic Medical Center at the University of Amsterdam, Amsterdam, The Netherlands.
Papers in Europe PMC - 07Gärtner J5 papers · 2021
Department of Pediatrics and Adolescent Medicine, University Medical Center Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, Germany.
Papers in Europe PMC - 08Poll-The BT5 papers · 2015
Department of Paediatric Neurology, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Meibergdreef 9, PO BOX 22660, 1105 AZ, Amsterdam, The Netherlands. b.t.pollthe@amc.uva.nl.
Papers in Europe PMC - 09Takashima S5 papers · 2021
Division of Genomics Research, Life Science Research Center, Gifu University, Gifu, Japan.
Papers in Europe PMC - 10van Grunsven EG5 papers · 2001
University Hospital Amsterdam, Academic Medical Center, Division of Clinical Chemistry, The Netherlands.
Papers in Europe PMC
Clinical research
Is a treatment being tested?
2
interventional trials for this specific condition
2 interventional trials matched this specific condition name; none in our sample are currently recruiting.
Data as of 27 July 2026
2 interventional trials — more than 73% of diseases in the trials denominator have none at all (5114 of 7003; this disease is at the 82.4th percentile).
medium confidence · 82.4th percentile (trials denominator)
Recruiting interventional trials
From the matched ClinicalTrials.gov set
2 interventional trials matched after quoted-phrase search and title/condition post-filter.
No currently recruiting studies in the matched set. Open the same search on ClinicalTrials.gov.
Observational and natural-history studies
1 observational study matches 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.
Recruiting or not-yet-recruiting
- NCT01668186·RECRUITING·Longitudinal Natural History Study of Patients With Peroxisome Biogenesis Disorders (PBD)
Conditions: Peroxisome Biogenesis Disorder · Zellweger Spectrum Disorder · RCDP - Rhizomelic Chondrodysplasia Punctata · D-Bifunctional Protein Deficiency·Matched via name phrase
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.
"Bifunctional enzyme deficiency" OR "D-bifunctional enzyme deficiency" OR "HSD17B4 deficiency" OR "d-bifunctional protein deficiency" OR "multifunctional enzyme deficiency" OR "peroxisomal multifunctional enzyme (MFE2) deficiency" OR "peroxisomal multifunctional enzyme deficiency" OR "pseudo-Zellweger syndrome"
ClinicalTrials.gov query (quoted phrases + MeSH via query.cond, plus recall-expansion terms when used):
"Bifunctional enzyme deficiency" OR "D-bifunctional enzyme deficiency" OR "HSD17B4 deficiency" OR "d-bifunctional protein deficiency" OR "multifunctional enzyme deficiency" OR "peroxisomal multifunctional enzyme (MFE2) deficiency" OR "peroxisomal multifunctional enzyme deficiency" OR "pseudo-Zellweger syndrome" OR "HSD17B4"
Recall-expansion terms: HSD17B4
Interventional trials matched via: phrase (mesh = registered under a MeSH descriptor no name phrase would catch; recall-expansion = gene / selected parent terms used only for trials).
Study-type breakdown: 2 interventional · 1 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
- "pseudo-Zellweger syndrome" also appears on ORPHA:2981
Ingested 2026-07-26T13:19:33.561Z