Wolfram syndrome

Wolfram syndrome, also called DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness), is a rare autosomal-recessive genetic disorder that causes childhood-onset diabetes mellitus, optic atrophy, and deafness as well as various other possible disorders including neurodegeneration. Symptoms can begin to appear as early as childhood to adult years (2–65 years old). There is a 25% recurrence risk in children.

It was first described in four siblings in 1938 by Dr. Don J. Wolfram, M.D. In 1995, diagnostic criteria were created based on the profiles of 45 patients. The disease affects the central nervous system (especially the brainstem). Wolfram syndrome is caused by pathogenic variants (mutations) in one of two genes — WFS1 or CISD2 — with the majority of patients carrying mutations in the WFS1 gene. The first causative gene for Wolfram syndrome, WFS1, was discovered by Dr. M. Alan Permutt, M.D. at Washington University in St. Louis. Wolfram syndrome was subsequently established as a prototype endoplasmic reticulum disorder caused by dysregulated unfolded protein response by Dr. Fumihiko Urano, M.D., Ph.D. at Washington University in St. Louis.

Fewer than 5,000 people in the US have this disease, with WFS1-Wolfram Syndrome being more common than CISD2-Wolfram Syndrome.