Mitochondria 1 myopathies : clinical defects 523

The mitochondrial myopathies are a clinically heterogeneous group o f diseases characterized by abnormal mitochondrial proliferation in skeletal muscle and in other affected cells [ 1, 2 ) . Studies of mitochondrial metabolism in vitro in over I00 published cases have identified a number of different functional defects which have mostly involved the oligomeric complexes of the mitochondria1 respiratory chain. In the majority of these patients, the defect was localized to complex 1 13, 41, complex 111 [ S ] or complex IV [6], but multiple enzyme defects [ 7-Y 1, as well as isolated deficiencies of complex I I 1101. and of the mobile carrier coenzyme Q,,, [ 111, have also been described. More recent strategies aimed at characterizing these diseases at a molecular and genetic level arc beginning to provide substance for the contention that defects in this pathway may be caused by mutations of nuclear or mitochondrial genes [3, 12-19). T h e fact that only about one in five patients has an affected relative 1201 would s u g e s t that the defect in some cases may be acquired. Viruses 12 1 ] and autoimmune mechanisms 1221 have been implicated, and the observation that 1 -methyl-4-phenylpyridium ( M P P + ) is a powerful inhibitor of complex I 12.31, and that complex I activity may be selectively impaired in patients with idiopathic Parkinson's disease [ 15. 241. suggests that environmental factors may also be involved. This paper summarizes clinical and biochemical data from S7 patients with mitochondrial myopathies, 46 of whom had