To determine the major causes of morbidity and mortality in the autosomal recessive Wolfram syndrome, which is defined by diabetes and bilateral progressive optic atrophy with onset in childhood or adolescence.

We abstracted and reviewed the medical records of 68 confirmed cases of Wolfram syndrome identified through a nationwide survey of endocrinologists, ophthalmologists, institutes, and homes for the blind. We also reviewed all available autopsy records.

The most common causes of morbidity and mortality were the neurological manifestations of this syndrome and the complications of urinary tract atony. There was a lower frequency of diabetic ketoacidosis, no histologically proven diabetic glomerulosclerosis, and less severe, more slowly progressive, diabetic retinopathy than in classic type I diabetic patients. Mortality in Wolfram syndrome is much higher than in type I diabetes; 60% of Wolfram syndrome patients die by age 35. Recognition of these clinical differences from classic type I diabetes is important for the proper management of Wolfram syndrome patients.

Identification of Wolfram syndrome patients among all diabetic patients presenting in childhood or adolescence is important because the management of patients with this syndrome is different from that of patients with classic type I diabetes.