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ORPHA:300

Bifunctional enzyme deficiency

low confidenceDisorder

Publications

1,906

Trials

2

Interventional, condition-specific

Researchers

1,331

Distinct authors in sample

Gene link

HSD17B4

Definitive

Readiness

5/6

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.

Orphanet entry

Cross-references

Joined from Mondo / Orphanet. MeSH labels may enter searches; UMLS / OMIM / NCIT are stored for reference.

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.”

5/6 stages with a signal

An interventional trial matched this condition name on ClinicalTrials.gov — see trials below.

  1. Gene identifiedPresent

    Definitive — HSD17B4

  2. LiteraturePresent

    1,906 matched papers (1,235 in last 10 years) Source

  3. Phenotype characterisedPresent

    60 HPO annotations (e.g. Hypertelorism; Very long chain fatty acid accumulation; Decreased nerve conduction velocity) Source

  4. Animal modelPresent

    4 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 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)

60

Associated phenotypes · MONDO:0009855

  • Hypertelorism
  • Very long chain fatty acid accumulation
  • Decreased nerve conduction velocity
  • Low-set ears
  • Primary adrenal insufficiency

Showing 5 of 60 — open Monarch for the full list.

Animal models (Monarch / Alliance)

4

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?

1,906

1,906 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.

1,906 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).

1,235 in the last 10 years · low confidence

Phrase hits: 321 · MeSH hits: 0

Open Europe PMC search

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.

  1. 01
    Wanders RJ20 papers · 2015

    Dept. of Pediatrics, University Hospital Amsterdam, The Netherlands.

    Papers in Europe PMC
  2. 02
    Ferdinandusse 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
  3. 03
    Shimozawa N8 papers · 2021

    Division of Genomics Research, Life Science Research Center, Gifu University, Gifu, Japan.

    Papers in Europe PMC
  4. 04
    Suzuki Y8 papers · 2001

    Department of Pediatrics, Gifu University School of Medicine.

    Papers in Europe PMC
  5. 05
    Wang Y7 papers · 2025

    Department of Molecular & Human Genetics, Baylor College of Medicine, and Baylor Genetics Laboratories, Houston, Texas, USA.

    Papers in Europe PMC
  6. 06
    Waterham HR6 papers · 2020

    Laboratory Genetic Metabolic Diseases, Academic Medical Center at the University of Amsterdam, Amsterdam, The Netherlands.

    Papers in Europe PMC
  7. 07
    Gärtner J5 papers · 2021

    Department of Pediatrics and Adolescent Medicine, University Medical Center Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, Germany.

    Papers in Europe PMC
  8. 08
    Poll-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
  9. 09
    Takashima S5 papers · 2021

    Division of Genomics Research, Life Science Research Center, Gifu University, Gifu, Japan.

    Papers in Europe PMC
  10. 10
    van 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 11 September 2026 · last trial check 28 July 2026

2 interventional trials — more than 77.2% of diseases in the trials denominator have none at all (5501 of 7126; this disease is at the 84.5th percentile).

low confidence · 84.5th 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

Open the complete matched search on ClinicalTrials.gov

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 Bifunctional enzyme 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.

("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" OR "HSD17B4 syndrome" OR "HSD17B4-related")

Run this search on Europe PMC

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"

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: 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
  • "pseudo-Zellweger syndrome" also appears on ORPHA:2981
  • Publication count (1906) is implausibly high for prevalence class "<1 / 1 000 000" — treat as possible over-matching, not a measure of research intensity

Ingested 2026-07-26T13:19:33.561Z