Wolfram syndrome: Portuguese research

Endokrynol Pol. 2021;72(4):353-356. doi: 10.5603/EP.a2021.0038. Epub 2021 May 19.


Introduction: Wolfram syndrome (WFS) is a neurological and endocrinological degenerative disorder, also known as DIDMOAD (Diabetes Insipidus, early-onset Diabetes Mellitus, progressive Optic Atrophy, and Deafness) syndrome. It is an autosomal recessive disorder, mostly involving the Wolfram syndrome 1 gene (WFS1). The phenotypic pleiomorphism, rarity, and molecular complexity complicate the follow-up of these patients.

Material and methods: We aimed to describe the clinical characteristics and the follow-up of 11 patients with this disorder. We retrospectively analysed all WFS patients diagnosed between 1990 and 2020 in the Centro Hospitalar São João, a tertiary hospital in Northern Portugal.

Results: Eleven patients were included. Four patients had all 4 components of DIDMOAD. The presentation was diabetes mellitus (DM) in 9 patients, optic atrophy (OA) in another patient, and diabetes insipidus (DI) in another one. The median age of DM and OA diagnosis was 6 and 14 years, respectively. Nine patients had diabetes mellitus, and the other 2 patients had impaired glucose tolerance. All patients had OA. Four patients presented DI, all of them diagnosed in adolescence. Four patients had hearing impairment, 5 had urological abnormalities, 5 had neurological disorders, and 8 had psychiatry disorders. Eight patients had a broad spectrum of recessive mutations in WFS1.

Conclusion: The information obtained in this study can facilitate further research in an attempt to improve prevention strategies for this devastating disease.

Keywords: Wolfram syndrome; deafness; diabetes insipidus; diabetes mellitus; optic atrophy.

MeSH terms

  • Adolescent
  • Child
  • Diabetes Insipidus*
  • Humans
  • Membrane Proteins / genetics
  • Optic Atrophy* / genetics
  • Portugal
  • Retrospective Studies
  • Wolfram Syndrome* / diagnosis
  • Wolfram Syndrome* / genetics


  • Membrane Proteins