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 Author s either in this syndrome or in similar genetic syndromes and to evalu ate the frequency of the main clinical features of the disease in an I talian population. We abstracted and reviewed the medical records of 1 8 patients with at least two of the most salient Wolf ram syndrome cli nical features, recruited from 10 Italian Centers. Mitochondrial DNA f rom the patients' blood was examined for the 3243 tRNA-LEU point mutat ion and for the 7.6 and 8.5 Kb deletions. Diabetes mellitus was the mo st frequent clinical manifestation (100%), followed by optic atrophy ( 89%), deafness (83%), diabetes insipidus (55%), urinary tract dilatati on (50%) and primary hypogonadism (11%). Other less common clinical fe atures 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 mitochondri al DNA deletions or the 3243 point mutation are not involved in the ae tiology of Wolfram syndrome in our patients; b) the frequency of the f our salient clinical features in this Italian population is very simil ar to that recently reported by others in the United Kingdom; c) urina ry tract abnormalities should be included among the typical clinical m anifestations of this syndrome. Diab. Nutr. Metab. 11: 114-120, 1998. (C) 1998, Editrice Kurtis.