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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Exercise intolerance and the mitochondrial respiratory chain.

The syndrome of exercise intolerance, cramps, and myoglobinuria is a common presentation of metabolic myopathies and has been associated with several specific inborn errors of glycogen or lipid metabolism. As disorders in fuel utilization presumably impair muscle energy production, it was more than a little surprising that exercise intolerance and myoglobinuria had not been associated with defects in the mitochondrial respiratory chain, the terminal energy-yielding pathway. Recently, however, specific defects in complex I, complex III, and complex IV have been identified in patients with severe exercise intolerance with or without myoglobinuria. All patients were sporadic cases and all harbored mutations in protein-coding genes of muscle mtDNA, suggesting that these were somatic mutations not affecting the germ-line. Another respiratory chain defect, primary coenzyme Q10 (CoQ10) deficiency, also causes exercise intolerance and recurrent myoglobinuria, usually in conjunction with brain symptoms, such as seizures or cerebellar ataxia. Primary CoQ10 deficiency is probably due to mutations in nuclear gene(s) encoding enzymes involved in CoQ10 biosynthesis.[1]


  1. Exercise intolerance and the mitochondrial respiratory chain. DiMauro, S. Italian journal of neurological sciences. (1999) [Pubmed]
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