trialregister.nlIdentifier: NTR1780.

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The phenotype of diabetes in MIDD appears to be independent of HLA-DQ phenotype and degree of heteroplasmy in leucocyte and oral mucosa DNA indicating that other, as yet unknown, factors modulate clinical expression of the 3243 mutation.

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Purpose:To investigate high-energy phosphate metabolism in striated skeletal muscle of patients with Maternally Inherited Diabetes and Deafness (MIDD) syndrome. Materials and Methods:In 11 patients with the MIDD mutation (six with diabetes mellitus [DM] and five non-DM) and eight healthy subjects, phosphocreatine (PCr) and inorganic phosphate (Pi) in the vastus medialis muscle was measured immediately after exercise using 31 P-magnetic resonance spectroscopy (MRS). The half-time of recovery (t1/2) of monoexponentially fitted (PCrϩPi)/PCr was calculated from spectra obtained every 4 seconds after cessation of exercise. A multiple linear regression model was used for statistical analysis. Results:Patients with the MIDD mutation showed a significantly prolonged t1/2 (PCrϩPi)/PCr after exercise as compared to controls (13.6Ϯ3.0 vs. 8.7Ϯ1.3 sec, P ϭ 0.01). No association between the presence of DM and t1/2 (PCr ϩ Pi)/PCr was found (P ϭ 0.382). THE MATERNALLY INHERITED DIABETES AND DEAFNESS (MIDD) syndrome is known as a phenotype of the adenosine to guanine mutation at position 3243 (A3243G) in the tRNA gene (1,2). The key identifying features of MIDD patients are characterized by a triad of diabetes mellitus (DM), developing in 80% of patients with the MIDD mutation carriers, sensorineural deafness, and a history of these conditions in maternal relatives (4 -7). Diagnosis of the MIDD syndrome is based on the pattern of inheritance, the presence of clinical features, and DNA analysis. Although MIDD is often unrecognized, it is estimated that MIDD affects between 0.6%-1.5% of DM patients (3). ConclusionBesides the characteristic triad, MIDD patients may present with other symptoms such as renal disease, cardiomyopathy, gastrointestinal complaints, and muscle cramps or muscle weakness (4).A transition of adenosine to guanine at nucleotide position 3243 affects the encoding of mitochondrial proteins. This mutation causes the formation of dysfunctional mitochondria and subsequently reduced mitochondrial oxidative adenosinetriphosphate (ATP) energy production (5). The striated skeletal muscle depends largely on mitochondrial oxidative phosphorylation for generation of high-energy phosphates. Associations have been suggested between (sub)clinical myopathies and mitochondrial dysfunction in the MIDD syndrome (6,7).Phosphorus-31 magnetic resonance spectroscopy ( 31 P-MRS) is a sensitive and specific noninvasive method for the assessment of skeletal muscle mitochondrial ATP production. Observations at rest are not specific for mitochondrial disorders. During exercise patients with mitochondrial myopathies will display rapid phosphocreatine (PCr) depletion. During recovery, 31 P-MRS measurements are the most sensitive and the most specific indices used to assess skeletal muscle mitochondrial ATP production (8 -11). To our knowledge, only a limited number of MIDD patients have been studied by skeletal muscle 31 P-MRS and the potential confounding effect of the presence of DM has not been systematically evaluated before (12)(13)...