To describe a case of Wolfram syndrome (WS) misdiagnosed as multiple sclerosis (MS) for over a decade.

MS is an autoimmune disease of the central nervous system characterized by inflammation and neurodegeneration. The McDonald’s Criteria is used to diagnose MS; however, studies indicate upwards of a third of new patients referred to subspecialty centers for MS are ultimately diagnosed with a mimicker. 

WS is an autosomal recessive disorder due to a mutation in the WFS1 gene, which encodes a transmembrane protein. WS is characterized by diabetes (type 1 or insipidus), optic nerve atrophy, hearing loss, and neurodegeneration. Given its rarity, WS is poorly recognized, and its symptomatology is often misattributed to other etiologies.

Case Report/literature review

A 53-year-old male with adult-onset type 1 diabetes mellitus and peripheral neuropathy presents to establish care.  MS was diagnosed a decade earlier following an episode of vertigo and MRI revealed numerous white matter lesions. Patient was placed on fingolimod shortly after diagnosis and later developed choroidal malignant melanoma.  MRI showed that white matter lesions did not fulfill Barkhof radiographic criteria. Review of past spinal fluid did not show markers of intrathecal synthesis. Family history was significant for optic nerve atrophy and genetic testing revealed pathogenic variants of WFS1.

MS is commonly misdiagnosed, which affects morbidity/mortality. A diverse group of pathologies can mimic MS, but genetic disorders are challenging to recognize. Our case highlights the consequences of a decade of unnecessary immunotherapy, possibly contributing to the development of melanoma—a known association with fingolimod. Strict adherence to the McDonald’s Criteria prevents over-diagnosis, but clinicians must also consider atypical history and MRI as well as unsupportive spinal fluid studies as red flags. A family history of diabetes, hearing loss and optic nerve atrophy should raise suspicion for Wolfram Syndrome and prompt genetic testing.