Screening the mitochondrial DNA of a 64-year-old woman with mitochondrial myopathy revealed 76% of the tRNA Leu(UUR) A3302G mutation in muscle. Muscle of her affected son carried 96% mutated mitochondrial DNA. Both patients were biopsied twice, showing isolated complex I deficiency in the son's first biopsy, additional increased (within normal range) complex II+III activities in his second biopsy, combined complex I, II+III deficiency in mothers first biopsy and additional complex IV deficiency in her second biopsy. After a stay in the mountains, the son died of cardiac arrhythmia. The A3302G mutation has been reported before and is associated with mitochondrial myopathy and cardiorespiratory failure. Pathogenesis is explained by abnormal mtRNA processing, which was also reported for the adjacent C3303T mutation associated with cardiomyopathy and/or skeletal myopathy. Our findings suggest that a high mutation load of the A3302G mutation can lead to fatal cardiorespiratory failure, likely triggered by low environmental oxygen pressure and exercise.

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Neuromuscular Disorders
Department of Neurology

van den Bosch, B, de Coo, I.F.M, Hendrickx, A, Busch, H.F.M, de Jong, G, Scholte, H.R, & Smeets, H.J.M. (2004). Increased risk for cardiorespiratory failure associated with the A3302G mutation in the mitochondrial DNA encoded tRNA Leu(UUR) gene. Neuromuscular Disorders, 14(10), 683–688. doi:10.1016/j.nmd.2004.06.004