Mitochondrial DNA studies and clinical findings in Wolfram syndrome: An Italian multicenter survey

The aim of this study was to verify the presence in Wolfram (DIDMOAD) syndrome of some mitochondrial DNA abnormalities found by other Authors either in this syndrome or in similar genetic syndromes and to evaluate the frequency of the main clinical features of the disease in an Italian population. We abstracted and reviewed the medical records of 18 patients with at least two of the most salient Wolfram syndrome clinical features, recruited from 10 Italian Centers. Mitochondrial DNA from the patients' blood was examined for the 3243 tRNA-LEU point mutation and for the 7.6 and 8.5 Kb deletions. Diabetes mellitus was the most frequent clinical manifestation (100%), followed by optic atrophy (89%), deafness (83%), diabetes insipidus (55%), urinary tract dilatation (50%) and primary hypogonadism (11%). Other less common clinical features were thiamine-responsive megaloblastic anemia and epilepsy. In all cases we failed to detect the 3243 point mutation and the 7.6 and 8.5 Kb deletions. We conclude that: a) the 7.6 and 8.5 Kb mitochondrial DNA deletions or the 3243 point mutation are not involved in the aetiology of Wolfram syndrome in our patients; b) the frequency of the four salient clinical features in this Italian population is very similar to that recently reported by others in the United Kingdom; c) urinary tract abnormalities should be included among the typical clinical manifestations of this syndrome.