Don J. Wolfram, MD, and a colleague first reported this condition (sometimes called DIDMOAD) in 1938. Since then, based on genetic studies and clinical features, at least three types have been described, all of which are hereditary multisystem disorders.
The essential features of Wolfram syndrome 2 disease are progressive damage to the optic nerve in association with type 1 or insulin dependent diabetes mellitus. Optic nerve damage may lead to the first symptoms, that of visual difficulties. However, a large number of additional features are usually present including hearing loss, anemia, seizures and behavioral changes. Unsteadiness (ataxia), anemia, seizures, and a variety of mental changes including depression, anxiety, dementia, and behavioral disorders are sometimes seen. Upper intestinal ulcer disease has been noted in several families. The kidney tubes (ureters) may be dilated.
Some clinical signs such as visual difficulties and diabetes may have their onset in the first year of life but may begin later. Vision loss can be rapid with legal blindness occurring in 8-10 years after the onset of symptoms. The brainstem may suffer degeneration as well and can be responsible for breathing difficulties that can lead to a fatal outcome by the age of 30 years.
The clinical picture is highly variable and not all signs and symptoms are present in all patients.
This is an autosomal recessive disorder that requires the presence of two mutations for the disease to appear. Parents who carry a single mutant copy and are clinically normal can expect that on average 25% of their children will inherit Wolfram syndrome.
The diagnosis can be made by multiple specialists because of the multisystem nature of this disorder. The prognosis is poor as most features are progressive and death by the age of 30 years is not uncommon. There is no treatment for the basic disease.