PHENOTYPIC-EXPRESSION OF DIABETES SECONDARY TO A T14709C MUTATION OF MITOCHONDRIAL-DNA - COMPARISON WITH MIDD SYNDROME (A3243G MUTATION) - A CASE-REPORT

OBJECTIVE - To analyze the clinical and biochemical features of a rece ntly described point mutation of mitochondrial DNA associated with dia betes. This mutation, characterized by a T14709C transition of a highl y conserved nucleotide in the region coding for the glutamic acid tRNA , is heteroplasmic. RESEARCH DESIGN AND METHODS - The phenotypic expre ssion in the insulin-requiring diabetic proband from the pedigree was compared to that of diabetic probands from three families with the cla ssic A3243G mtDNA mutation (maternally inherited diabetes and deafness [MIDD] syndrome). The same investigations to evaluate pancreatic neur osensorial and muscle involvement were performed in all four patients. RESULTS - The natural courses of the diabetes and the hearing defects were not different between the two mutations. The patient with the 14 709 mutation, however, exhibited a milder alteration of pigmentary epi thelium of retina and a much more severe muscle involvement, as attest ed by the clinical expression and the concurrent anomalies of muscle e nergy production evidenced by P-31 magnetic resonance spectroscopy, co nfirming the profound impairment of oxidative processes. CONCLUSIONS - This novel mutation has to be added to the other known mtDNA anomalie s in order to ascribe some diabetes suspected to arise from mitochondr ial defects to this nosological framework.