OBJECTIVE

A point mutation in the mitochondrial genome has been identified as a cause of diabetes and deafness. We report two pedigrees with and A-to-G transition at nucleotide 3243 of mtDNA within the tRNALeu(UUR) gene and focus our investigations on other localizations of the anomaly, particularly muscle and retina.

RESEARCH DESIGN AND METHODS

Muscular localization has been studied in probands by invasive and noninvasive methods, including muscle biopsy (evaluation of the proportion of mutated mtDNA in comparison to blood cells, measurement of respiratory chain complex activities and histological and histochemical aspects) and 31P-nuclear magnetic resonance (NMR) spectroscopy. Ophthalmic and angiographic examination of retina, electroretinography, and visual evoked potentials were performed in five subjects.

RESULTS

This mutation, previously described in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), was expressed more abundantly in muscle than in nucleated blood cells. This low expression in blood cells could hamper the diagnosis for some patients. In addition, despite poor clinical expression, muscle was found to be highly affected. Ragged red fibers and dystrophic mitochondria were observed in muscle biopsy. Histochemical assays showed decreased activity of respiratory chain complexes, and 31P-NMR in vivo data further confirmed the defect of muscle oxidative processes. Exercise-induced lactate production was increased. Finally, in both families, an atypical “salt and pepper” pigmentary retinopathy was observed without consequences on visual acuity.

CONCLUSIONS

In diabetes secondary to 3243 mtDNA mutation, infraclinical muscular and ocular lesions are frequent. These two locations of the disease, which are easily investigated by simple methods, can help in the diagnosis of this new type of diabetes.

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