ESPE Abstracts

Wolfram Syndrome Type 1 also known as DIDMOAD syndrome is an autosomal recessive genetic disorder, characterized by major criteria diabetes mellitus and optic atrophy under the age of 16, as well as minor criteria diabetes insipidous, optic atrophy and diabetes mellitus over the age of 16 years deafness, neurological signs, renal tract structural or function abnormalities, loss of function mutation in WFS1 or CISD2 gene and or family with Wolfram syndrome. Other features could be hypogonadism (by male patients), absence of type 1 diabetes mellitus autoantibodies, bilateral cataract and gastrointestinal disorders. Today it is established, that the gene WFS1 or Wolframin gene is responsible for Wolfram syndrome Type 1. It codes for the homonym protein Wolframin which is found in endoplasmic reticulum, especially in cells of heart, brain, lungs, inner ear and pancreas. The function of Wolframin is unknown. It is speculated, that Wolframin may help fold protein precursor of insulin and may help maintain the cellular lever of calcium ions. Up today more than 30 WSF1 mutations are identified. Type of Wolfram Syndrome is caused by mutations in the gene CISD2. CISD2 stands for CDGSH iron sulfur domain 2 a protein found in the outer membrane of mitochondria. It is demonstrated, that it is involved in mammalian live span control. The prevalence of the disease is between 1-9/ 1 000 000 and the first symptoms manifest in the childhood. We report on a 17 year old patient, refugee from Syria, who initially presented with Diabetes mellitus Type 1 since the age of 6 years. We then diagnosed deafness and depression. A cranial MRT showed optic nerve atrophy. The discovery of a mutation in WFS1 gene (c.1546_1546delTTC;p.Phe516del) confirmed our diagnosis. Interestingly his 3 older sisters in Jordan hat similar symptoms, as well as renal tract structural anomalies and sensomotoric neuropathy and epilepsy. This case reminds us, that patients, who present with the combination of diabetes mellitus, deafness and visual impairment are serious candidates for Wolfram Syndrome. Occurrence of type-1-diabetes mellitus in our patient is exceptional. Not all symptoms may manifest during childhood, therefore continuous awareness is mandatory.