ESPE Abstracts

Context: Wolfram syndrome (WS) is an autosomal recessive neurodegenerative disorder caused by mutations in the WFS1 gene characterized by central diabetes insipidus, juvenile-onset diabetes mellitus (DM), optic atrophy (OA), and deafness. The natural history of WS is variable, even within the same family and with the same mutation.

Objective: The aimof this study is to report the phenotypes of five patients of Druze origin, all carrying the same autosomal recessive mutation in the WSF1 gene.

Patients & Methods: Five patients belonging to three core families were enrolled. Clinical, biochemical, and genetic data were retrieved retrospectively from their medical files.

Results: All five patients carried the same homozygous WSF1 mutation c.2649del, p.Phe884fs. In all patients, the first presentation was DM at a mean age of 5 years 2 months (range 4–7 years), diagnosed initially as type 1 DM and treated with insulin. Anti-pancreatic autoantibodies were negative. All five patients had OA that appeared at a mean age of 12 years 3 months (range 4–30 years). None had diabetes insipidus and three had hearing loss and neurological disorders.

Conclusion: This is the first report of a founder mutation in the WFS1 gene in the Druze population in Israel. Our findings imply that molecular analysis is warranted in children presenting with DM with negative pancreatic antibodies and additional organ involvement, particularly in consanguineous families. Early diagnosis of WS is important for therapeutic approaches, especially if novel medications become available, and for familial genetic consultation.