ORPHA:3463
Wolfram syndrome
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
Query health: suspect — Only one of 2 strategies returned hits (phrase).
Publications
2,431
94.2th percentile
Trials
7
Interventional, condition-specific
Researchers
1,108
Distinct authors in sample
Gene link
CISD2, WFS1
Definitive
Readiness
3/6
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.
Cross-references
Joined from Mondo / Orphanet. MeSH labels may enter searches; UMLS / OMIM / NCIT are stored for reference.
- MONDO:0018105
- MeSH:D014929
- UMLS:C0043207
- NCIT:C35133
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.”
3/6 stages with a signal
An interventional trial matched this condition name on ClinicalTrials.gov — see trials below.
- Gene identifiedPresent
Definitive — CISD2, WFS1
- LiteraturePresent
2,431 matched papers (1,333 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
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)
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?
2,431
2,431 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=5449) is 41.
2,431 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).
1,333 in the last 10 years · medium confidence · 94.2th percentile (publications denominator)
Phrase hits: 2,431 · MeSH hits: 0
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.
- 01Urano F14 papers · 2026
Division of Endocrinology, Metabolism & Lipid Research, Washington University, St. Louis, MO 63110, USA.
Papers in Europe PMC - 02Esteban-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 - 03Hershey 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 - 04Tang AF6 papers · 2026
Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States.
Papers in Europe PMC - 05Caruso V5 papers · 2024
Psychiatry 2 Unit, Clinical and Experimental Medicine Department, University of Pisa, 56126 Pisa, Italy.
Papers in Europe PMC - 06Fernández-Martínez JL5 papers · 2025
Group of Inverse Problems, Optimization and Machine Learning, Department of Mathematics, Oviedo University, 33007 Oviedo, Spain.
Papers in Europe PMC - 07Frontino 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 - 08Hurst 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 - 09Lugar HM5 papers · 2026
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States.
Papers in Europe PMC - 10Rigoli 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 27 July 2026
7 interventional trials — more than 73% of diseases in the trials denominator have none at all (5114 of 7003; this disease is at the 89.9th percentile).
medium confidence · 89.9th 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
- NCT07313085·NOT YET RECRUITING·Mechanisms of Fecal Incontinence in Wolfram Syndrome
Conditions: Wolfram Syndrome · Fecal Incontinence·Matched via name phrase
- NCT03988764·RECRUITING·Monogenic Diabetes Misdiagnosed as Type 1
Conditions: Diabetes Mellitus, Type 1 · Monogenic Diabetes · Neonatal Diabetes · Maturity-onset Diabetes in the Young (MODY)·Matched via name phrase
- NCT07336966·NOT YET RECRUITING·Does Recessive Optic Atrophy Due to WFS1 Exist?
Conditions: Wolfram Syndrome 1 · Optic Atrophies, Hereditary·Matched via name phrase
- NCT02841553·RECRUITING·Wolfram Syndrome and WFS1-related Disorders International Registry and Clinical Study
Conditions: Wolfram Syndrome · Diabetes Mellitus · Optic Nerve Atrophy · Deafness·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.
"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"
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" OR "CISD2" OR "WFS1"
Recall-expansion terms: CISD2, WFS1
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: suspect — strategies attempted: phrase, recall-expansion; 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