Wolfram syndrome is an extremely rare neurodegenerative disorder characterized by diabetes mellitus, optic atrophy, deafness, and diabetes insipidus. Affected patients present with juvenile onset diabetes mellitus, and optic atrophy. A large number of these patients also develop diabetes insipidus, and/or sensorineural deafness. The optic atrophy is progressive, and most patients become blind by the age of 8-years. In addition, patients may also show neurological symptoms, such as ataxia and startle myoclonus, psychological complications, problems with digestion, and renal complications. The disorder is rare, with only about 170 people affected people having been reported till date.

The WFS1 gene has been implicated in the pathogenesis of Wolfram Syndrome. This gene, located on chromosome 4, codes for a protein known as wolframin. Although the exact function of this protein is not known, its localization within the endoplasmic reticulum seems to suggest that it may play a role in protein folding and post-translational modifications. A high level of expression of this gene is specially noticed in the pancreas, giving rise to the theory that wolframin may be involved in the folding of the pre-proinsulin molecule, thereby explaining defects in the gene leading to diabetes. In addition, several mutations within the WFS1 gene have been implicated in other forms of sensorineural deafness too. A probable explanation put forward is that the protein may help in maintaining the levels of calcium ions in the inner ear.