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ORPHA:773

Adult Refsum disease

high confidenceDisorder

Also known as: Classic Refsum disease · HMSN 4 · HMSN IV · Hereditary motor and sensory neuropathy type 4 · Hereditary motor and sensory neuropathy type IV · Heredopathia atactica polyneuritiformis · Phytanic-CoA hydroxylase deficiency

Publications

3,541

88.8th percentile

Trials

3

Interventional, condition-specific

Researchers

1,101

Distinct authors in sample

Gene link

PHYH

Definitive

Readiness

5/6

Stages with a signal

Clinical definition (Orphanet)

A disease characterized by anosmia, cataract, early-onset retinitis pigmentosa and possible neurological manifestations, including peripheral and cerebellar . Other features can be deafness, ichthyosis, skeletal abnormalities, and cardiac arrhythmia. It is characterized biochemically by accumulation of phytanic acid in plasma and tissues.

How rare: 1-9 / 1 000 000 — roughly one to nine people per million. In a city the size of Kolkata, perhaps a few dozen.

Orphanet entry

Cross-references

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

Additional Mondo synonyms (17)

HMSN type IV · HSMN IV · Refsum Disease · Refsum disease · Refsum disease, adult, 1 · Refsum disease, classic · Refsum's disease · adult Refsum disease · adult Refsum disease due to PHYH · classic Refsum disease · hereditary motor and sensory neuropathy 4 · hereditary motor and sensory neuropathy type 4 · hereditary sensory and motor neuropathy type 4 · heredopathia atactica polyneuritiformis · hypertrophic neuropathy of Refsum · phytanic acid oxidase deficiency · phytanic-CoA hydroxylase 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.”

5/6 stages with a signal

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

  1. Gene identifiedPresent

    Definitive — PHYH

  2. LiteraturePresent

    3,541 matched papers (1,299 in last 10 years) Source

  3. Phenotype characterisedPresent

    65 HPO annotations (e.g. Retinopathy; Cataract; Cardiomyopathy) Source

  4. Animal modelPresent

    2 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

    3 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 (PHYH).

GenCC classification: Definitive.

Phenotypes (Monarch / HPO)

65

Associated phenotypes · MONDO:0009958

  • Retinopathy
  • Cataract
  • Cardiomyopathy
  • Miosis
  • Hypotonia

Showing 5 of 65 — open Monarch for the full list.

Animal models (Monarch / Alliance)

2

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)

2 associated chemicals · 5 pathways. Therapeutic evidence is listed first when present — not a treatment recommendation.

  • Orlistat · therapeutic
  • Phytanic Acid · marker/mechanism

Pathways: Peroxisome; Metabolism; Alpha-oxidation of phytanate; Peroxisomal lipid metabolism; Metabolism of lipids and lipoproteins

MyDisease.info · MONDO:0009958

Literature

Is anyone studying this?

3,541

3,541 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.

3,541 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).

1,299 in the last 10 years · high confidence · 88.8th percentile (publications denominator)

Phrase hits: 1,926 · MeSH hits: 29

Open Europe PMC search

Who's working on it?

1,101

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
    Gibberd FB16 papers · 2010

    Refsum's Disease Clinic, Chelsea & Westminster Hospital, 369 Fulham Road, London SW10 9NH, UK.

    Papers in Europe PMC
  2. 02
    Billimoria JD7 papers · 1989
    Papers in Europe PMC
  3. 03
    Wierzbicki AS7 papers · 2026

    Department of Chemical Pathology, St. Thomas' Hospital, London, UK. Anthony.Wierzbicki@kcl.ac.uk

    Papers in Europe PMC
  4. 04
    Clemens ME6 papers · 1989
    Papers in Europe PMC
  5. 05
    Sidey MC6 papers · 2010
    Papers in Europe PMC
  6. 06
    Wanders RJA6 papers · 2025

    Laboratory Genetic Metabolic Diseases, Department of Clinical Chemistry, Amsterdam UMC, Location AMC, University of Amsterdam, The Netherlands.

    Papers in Europe PMC
  7. 07
    Feher MD5 papers · 2016

    Adult Refsum Disease Clinic, Chelsea & Westminster Hospital, London, UK.

    Papers in Europe PMC
  8. 08
    Leroy BP5 papers · 2026

    Department of Ophthalmology, Ghent University and Ghent University Hospital, Corneel Heymanslaan 10, 9000 Ghent, Belgium.

    Papers in Europe PMC
  9. 09
    Michaelides M4 papers · 2025

    Moorfields Eye Hospital NHS Foundation Trust, London, UK.

    Papers in Europe PMC
  10. 10
    Waterham HR4 papers · 2023

    Laboratory Genetic Metabolic Diseases, Department of Clinical Chemistry, Amsterdam UMC, Location AMC, University of Amsterdam, The Netherlands.

    Papers in Europe PMC

Clinical research

Is a treatment being tested?

3

interventional trials for this specific condition

3 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

3 interventional trials — more than 77.2% of diseases in the trials denominator have none at all (5501 of 7126; this disease is at the 86.7th percentile).

high confidence · 86.7th percentile (trials denominator)

Recruiting interventional trials

From the matched ClinicalTrials.gov set

3 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

3 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.

Recruiting or not-yet-recruiting

Open the complete matched search on ClinicalTrials.gov

General rare disease registries you may be eligible for

These studies enroll across many rare conditions. They are not counted as evidence that anyone is studying this specific disease.

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 3 · after dedupe 3 · already on CT.gov 0 · kept 0 · parent 0 · uncertain 3 · 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).

Uncertain / not reviewed (3)

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 Adult Refsum disease — 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.

("Adult Refsum disease" OR "Classic Refsum disease" OR "HMSN 4" OR "HMSN IV" OR "Hereditary motor and sensory neuropathy type 4" OR "Hereditary motor and sensory neuropathy type IV" OR "Heredopathia atactica polyneuritiformis" OR "Phytanic-CoA hydroxylase deficiency" OR "HMSN type IV" OR "HSMN IV" OR "Refsum Disease" OR "Refsum disease, adult, 1" OR "Refsum disease, classic" OR "Refsum's disease" OR "adult Refsum disease due to PHYH" OR "hereditary motor and sensory neuropathy 4" OR "hereditary sensory and motor neuropathy type 4" OR "hypertrophic neuropathy of Refsum" OR "hypertrophic neuropathy of the Refsum" OR "phytanic acid oxidase deficiency") OR (MESH:"Refsum disease with increased pipecolic acidemia" OR MESH:"Refsum Disease") OR ("PHYH" OR "PHYH syndrome" OR "PHYH-related")

Run this search on Europe PMC

MeSH descriptor terms unioned into the query: Refsum disease with increased pipecolic acidemia; Refsum Disease

ClinicalTrials.gov query (quoted phrases + MeSH via query.cond, plus recall-expansion terms when used):

"Adult Refsum disease" OR "Classic Refsum disease" OR "HMSN 4" OR "HMSN IV" OR "Hereditary motor and sensory neuropathy type 4" OR "Hereditary motor and sensory neuropathy type IV" OR "Heredopathia atactica polyneuritiformis" OR "Phytanic-CoA hydroxylase deficiency" OR "HMSN type IV" OR "HSMN IV" OR "Refsum Disease" OR "Refsum disease, adult, 1" OR "Refsum disease, classic" OR "Refsum's disease" OR "adult Refsum disease due to PHYH" OR "hereditary motor and sensory neuropathy 4" OR "hereditary sensory and motor neuropathy type 4" OR "hypertrophic neuropathy of Refsum" OR "hypertrophic neuropathy of the Refsum" OR "phytanic acid oxidase deficiency" OR "Refsum disease with increased pipecolic acidemia"

Interventional trials matched via: both, 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: 3 interventional · 3 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

Ingested 2026-07-26T15:18:21.233Z