A genetic neurodegenerative disease that leads to many different abnormalities including diabetes insipidus (inability to concentrate the urine), diabetes mellitus (the usual type of diabetes), blindness (due to optic atrophy, degeneration of the nerve to the eye), and deafness. Patients usually also suffer from severe abnormalities of the nervous system that can be accompanied by behavior problems, psychiatric hospitalizations and, in about a quarter of cases, suicide attempts.
Wolfram syndrome is sometimes referred to as “DIDMOAD” (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness). Only the insulin-dependent diabetes mellitus and optic atrophy are necessary to make the diagnosis.
The syndrome is inherited as an autosomal recessive trait so that brothers and sisters of a child with the syndrome each have a 25 percent chance of receiving the gene from both parents and therefore having the syndrome. The syndrome is caused by a mutation in the gene responsible for the production of a protein called wolframin, resulting in loss of function of this protein. The gene is in chromosome 4p16.1.
Wolfram syndrome is genetically heterogeneous (mixed). There is, for example, a type of Wolfram syndrome with additional atypical features such as profound upper gastrointestinal ulceration and bleeding as well as an absence of diabetes insipidus. The gene for this type of Wolfram syndrome is not in the region of chromosome 4p16.1 but rather is in chromosome 4q22-24.
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