Wolfram Syndrome and WFS1-related Disorders International Registry and Clinical Study
In this study, the investigators hypothesize that studying monogenic variants with strong effect associated with severe insulin deficiency of Wolfram syndrome will provide important insights into the more complex type 1 and type 2 diabetes mellitus. Aim 1. Establish and maintain a registry of patients with Wolfram syndrome. An Internet based registry will be employed to enroll participants with the clinical diagnosis of Wolfram syndrome (insulin dependent DM and bilateral OA). Clinical information regarding age of diagnosis and progression of the disease will be collated and analyzed to better define its natural history, along with potential metabolic phenotypes such as glucose intolerance of heterozygous parents and unaffected sibs. If not already completed, blood for WFS1 sequence analysis will be obtained on the participants (parents and sibs also for control purposes) and sent to a CLIA certified lab to define the mutation. This information will benefit patient families and referring physicians by providing a genetic diagnosis and where indicated. The Wolfram Syndrome Registry will foster international collaborations to more efficiently and systematically collect Wolfram syndrome patients and their clinical and experimental data.
⁃ Major Criteria
• Diabetes mellitus \<16 yrs
• Optic atrophy \<16 yrs
⁃ Minor Criteria
• Diabetes insipidus
• Diabetes mellitus \>16yrs
• Optic atrophy \>16 yrs
• Sensorineural deafness
• Neurological signs (ataxia, epilepsy, cognitive impairment)
• Renal tract abnormalities (structural or functional)
• 1 loss of function mutation in WFS1/CISD2 AND/OR family history of Wolfram syndrome
⁃ Minimum Required
• 2 major OR
• 1 major plus 2 minor criteria OR
• 2 pathological WFS1 or CISD2 mutations are identified
⁃ Other variable suggestive evidence
• Hypogonadism (males)
• An absence of type 1 diabetes auto-antibodies
• Bilateral cataracts
• Psychiatric disorder
• Gastrointestinal