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 recently described point mutation of mitochondrial DNA associated with diabetes. This mutation, characterized by a T14709C transition of a highly conserved nucleotide in the region coding for the glutamic acid tRNA, is heteroplasmic. RESEARCH DESIGN AND METHODS - The phenotypic expression in the insulin-requiring diabetic proband from the pedigree was compared to that of diabetic probands from three families with the classic A3243G mtDNA mutation (maternally inherited diabetes and deafness [MIDD] syndrome). The same investigations to evaluate pancreatic neurosensorial 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 14709 mutation, however, exhibited a milder alteration of pigmentary epithelium of retina and a much more severe muscle involvement, as attested by the clinical expression and the concurrent anomalies of muscle energy production evidenced by P-31 magnetic resonance spectroscopy, confirming the profound impairment of oxidative processes. CONCLUSIONS - This novel mutation has to be added to the other known mtDNA anomalies in order to ascribe some diabetes suspected to arise from mitochondrial defects to this nosological framework.