Phenotypic Expression of Diabetes Secondary to a T14709C Mutation of Mitochondrial DNA: Comparison with MIDD syndrome (A3243G mutation): a case report
- B H Vialettes, MD,
- V Paquis-Flucklinger, MD, PHD,
- J F Pelissier, MD,
- D Bendahan, PHD,
- H Narbonne,
- P Silvestre-Aillaud, MD,
- M F Montfort, PHD,
- M Righini-Chossegros, MD,
- J Pouget, MD,
- P J Cozzone, MD and
- C Desnuelle, MD
- Laboratoire de Neurobiologie Cellulaire, Centre Hôpital Universitairé Timone, Université de la Méditerranée Marseille, France
- Faculté de Médecine, Centre National de la Recherche Scientifique (CNRS) Unite Mixte de Recherche (UMR) 6549 et Université de Nice Sophia Antipolis Service de Nutrition, Maladies Métaboliques, Endocrinologie, Centre Hôpital Universitairé Timone, Université de la Méditerranée Marseille, France
- Hôpital Sainte-Marguerite (Unité Propre de Recherche de l'Enseignement Supérieur - Equipe d'Accueil [UPRES EA] 2193), Université de la Méditerranée; the Laboratoire de Neuropathologie, Centre Hôpital Universitairé Timone, Université de la Méditerranée Marseille, France
- Faculté de Médecine, Université de la Mediterranée; the Centre de Résonance Magnétique Biologique et Médicale, Centre Hôpital Universitairé Timone, Université de la Méditerranée Marseille, France
- Faculté de Médecine Marseille, CNRS UMR 6612 et Université de la Méditerranée; and the Service de Pathologie Neuro-musculaire, Centre Hôpital Universitairé Timone, Université de la Méditerranée Marseille, France
- Address correspondence and reprints requests to Pr. B. Vialettes, Service de Nutrition, Maladies Metaboliques, Endocrinologie, Hopital Sainte-Marguerite, 13274 Marseille Cedex 09, France.
Abstract
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 14,709 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 31P 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.
- Received February 13, 1997.
- Accepted July 17, 1997.
- Copyright © 1997 by the American Diabetes Association
