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ORPHA:3463

Wolfram syndrome

medium confidenceDisorder

Also known as: Arginine vasopressin deficiency- diabetes mellitus-optic atrophy-deafness syndrome · Arginine vasopressin deficiency- diabetes mellitus-optic atrophy-hearing loss syndrome · DIDMOAD syndrome · Diabetes insipidus-diabetes mellitus-optic atrophy-deafness syndrome · Diabetes insipidus-diabetes mellitus-optic atrophy-hearing loss syndrome

Publications

4,961

92.6th percentile

Trials

7

Interventional, condition-specific

Researchers

1,108

Distinct authors in sample

Gene link

CISD2, WFS1

Definitive

Readiness

6/6

Stages with a signal

Clinical definition (Orphanet)

A rare, genetic, endocrine disorder characterized by type I diabetes mellitus (DM), diabetes insipidus (DI), sensorineural deafness (D), bilateral optical atrophy (OA) and neurological signs.

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 (4)

DIDMOAD · diabetes insipidus, diabetes mellitus, optic atrophy, and deafness syndrome · diabetes insipidus-diabetes mellitus-optic atrophy-deafness syndrome · diabetes mellitus and insipidus with optic atrophy and deafness

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.”

6/6 stages with a signal

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

  1. Gene identifiedPresent

    Definitive — CISD2, WFS1

  2. LiteraturePresent

    4,961 matched papers (3,251 in last 10 years) Source

  3. Phenotype characterisedPresent

    101 HPO annotations (e.g. Abnormal bleeding; Neurogenic bladder; Decreased circulating immunoglobulin concentration) Source

  4. Animal modelPresent

    9 genotype models (Mus musculus, Danio rerio) Source

  5. Orphan designationPresent

    2 FDA · 4 EMA designations (2 FDA orphan-indication approvals) — e.g. dantrolene sodium Source

  6. Interventional trialPresent

    7 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 (CISD2, WFS1).

GenCC classification: Definitive.

Phenotypes (Monarch / HPO)

101

Associated phenotypes · MONDO:0018105

  • Abnormal bleeding
  • Neurogenic bladder
  • Decreased circulating immunoglobulin concentration
  • Impaired collagen-induced platelet aggregation
  • Diabetes insipidus

Showing 5 of 101 — open Monarch for the full list.

Animal models (Monarch / Alliance)

9

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)

6

Designations · 2 with FDA orphan-indication approval

  • FDA dantrolene sodiumWolfram Syndrome · 2016-02-17 · Not FDA Approved for Orphan Indication
  • FDA sodium valproateWolfram Syndrome · 2015-08-05 · Not FDA Approved for Orphan Indication
  • EMA sodium phenylacetate;ursodoxicoltaurineTreatment of Wolfram syndrome · 25/07/2024 · PositiveEMA designation
  • EMA liraglutideTreatment of Wolfram syndrome · 18/07/2022 · PositiveEMA designation
  • EMA sodium valproate fNorTreatment of Wolfram syndrome · 15/01/2015 · PositiveEMA designation
  • EMA Dantrolene sodiumTreatment of Wolfram syndrome · 12/12/2016 · WithdrawnEMA designation

Sources: FDA OOPD · EMA orphan designations

Open Targets candidates

5

Drugs / clinical candidates · MONDO_0018105

CTD chemicals (MyDisease.info)

No CTD chemical associations returned for this Mondo ID.

Literature

Is anyone studying this?

4,961

4,961 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.

4,961 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).

3,251 in the last 10 years · medium confidence · 92.6th percentile (publications denominator)

Phrase hits: 2,431 · MeSH hits: 0

Open Europe PMC search

Who's working on it?

1,108

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
    Urano F14 papers · 2026

    Division of Endocrinology, Metabolism & Lipid Research, Washington University, St. Louis, MO 63110, USA.

    Papers in Europe PMC
  2. 02
    Esteban-Bueno G9 papers · 2026

    UGC Almeria Periferia, Distrito Sanitario Almeria, Sistema Sanitario Publico Andaluz (SSPA), Consejeria de Salud y Consumo (Junta de Andalucia), Seville, Spain.

    Papers in Europe PMC
  3. 03
    Hershey T9 papers · 2026

    Department of Neurology, Washington University in St Louis School of Medicine, St Louis, Missouri, United States of America.

    Papers in Europe PMC
  4. 04
    Tang AF6 papers · 2026

    Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States.

    Papers in Europe PMC
  5. 05
    Caruso V5 papers · 2024

    Psychiatry 2 Unit, Clinical and Experimental Medicine Department, University of Pisa, 56126 Pisa, Italy.

    Papers in Europe PMC
  6. 06
    Fernández-Martínez JL5 papers · 2025

    Group of Inverse Problems, Optimization and Machine Learning, Department of Mathematics, Oviedo University, 33007 Oviedo, Spain.

    Papers in Europe PMC
  7. 07
    Frontino G5 papers · 2025

    Department of Pediatrics, Pediatric Diabetology Unit, Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Vita Salute San Raffaele University, Milan, Italy. frontino.giulio@hsr.it.

    Papers in Europe PMC
  8. 08
    Hurst S5 papers · 2026

    Division of Endocrinology, Department of Medicine, Metabolism, and Lipid Research, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO, 63110, USA.

    Papers in Europe PMC
  9. 09
    Lugar HM5 papers · 2026

    Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States.

    Papers in Europe PMC
  10. 10
    Rigoli L5 papers · 2024

    Department of Human Pathology of Adulthood and Childhood G. Barresi, University of Messina, 98125 Messina, Italy.

    Papers in Europe PMC

Clinical research

Is a treatment being tested?

7

interventional trials for this specific condition

7 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

7 interventional trials — more than 77.2% of diseases in the trials denominator have none at all (5501 of 7126; this disease is at the 90.9th percentile).

medium confidence · 90.9th percentile (trials denominator)

Recruiting interventional trials

From the matched ClinicalTrials.gov set

7 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

7 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

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 Wolfram syndrome — 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.

("Wolfram syndrome" OR "Arginine vasopressin deficiency- diabetes mellitus-optic atrophy-deafness syndrome" OR "Arginine vasopressin deficiency- diabetes mellitus-optic atrophy-hearing loss syndrome" OR "DIDMOAD syndrome" OR "Diabetes insipidus-diabetes mellitus-optic atrophy-deafness syndrome" OR "Diabetes insipidus-diabetes mellitus-optic atrophy-hearing loss syndrome" OR "DIDMOAD" OR "diabetes insipidus, diabetes mellitus, optic atrophy, and deafness syndrome" OR "diabetes mellitus and insipidus with optic atrophy and deafness") OR ("CISD2" OR "CISD2 syndrome" OR "CISD2-related" OR "WFS1" OR "WFS1 syndrome" OR "WFS1-related")

Run this search on Europe PMC

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

"Wolfram syndrome" OR "Arginine vasopressin deficiency- diabetes mellitus-optic atrophy-deafness syndrome" OR "Arginine vasopressin deficiency- diabetes mellitus-optic atrophy-hearing loss syndrome" OR "DIDMOAD syndrome" OR "Diabetes insipidus-diabetes mellitus-optic atrophy-deafness syndrome" OR "Diabetes insipidus-diabetes mellitus-optic atrophy-hearing loss syndrome" OR "DIDMOAD" OR "diabetes insipidus, diabetes mellitus, optic atrophy, and deafness syndrome" OR "diabetes mellitus and insipidus with optic atrophy and deafness"

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: 7 interventional · 7 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 short or not clearly distinctive
  • No synonyms dropped by stoplist
  • No label/synonym collisions with other diseases in this corpus

Ingested 2026-07-26T23:16:21.432Z