Wolfram syndrome: Clinical and genetic aspects

Wolfram syndrome, also known as DIDMOAD syndrome, was first described in 1938. It consists of a combination of diabetes insipidus, diabetes mellitus, optic atrophy, and deafness. A large number of other abnormalities also may develop, such as dilation of the urinary tract, neurologic disease, and psychiatric illness. These conditions are discovered during childhood and early adulthood, are progressive, and are often fatal. Pathologic studies confirm the neurodegenerative nature of the syndrome. Wolfram syndrome patients appear to be relatively resistant to the microvascular changes usually seen in diabetes. Several other endocrine disorders, particularly hypogonadism, have been reported. Significant advances have been made in the genetics of Wolf ram syndrome. Although the syndrome is inherited in an autosomal recessive fashion, deletions of the mitochondrial genome have been detected in some patients. Recent progress has revealed mutations of a gene on chromosome 4p16 in Wolfram syndrome patients. This gene has been named WFS1 and encodes a transmembrane protein of unknown function. The relationship between the nuclear DNA mutations and those of the mitochondria is not clear, but it is the subject of future study.