Mitochondrial myopathies: deficiencies localized to complex I and complex III of the mitochondrial respiratory chain.

Deficiencies of the mitochondrial respiratory chain or the phosphorylation system are becoming increasingly recognized causes of myopathy and multisystem disease in man. In biochemical terms, the ones most clearly defined have been associated with impaired activities of NADH : ubiquinone reductase (Morgan-Hughes el al., 1979, 1984; Land et al., 1981; Moreadith etal., 1984), ubiquino1:cytochrome c reductase (Spiro et al., 1970; Morgan-Hughes et al., 1977, 1982; Darley-Usmar et al., 1983), cytochrome c oxidase (DiMauro et al., 1985) and ATP synthase (Schotland et al., 1976; Clark et al., 1983). Although in most cases the biochemical error has been identified in isolated muscle mitochondria, myopathy may be overshadowed clinically by major involvement of other organs such as the brain, liver or heart. The morphological hallmark of these disorders is the so called ragged red muscle fibre (Olson et al., 1972), which owes its appearance in frozen sections stained with the modified Gomori trichrome method to large subsarcolemmal collections of structurally abnormal mitochondria (Morgan-Hughes & Landon, 1983). The diverse clinical expression of defects of this type is illustrated by four examples taken from a series of 30 patients investigated in our laboratories over the last few years. Of these 30 cases, the defect was localized to complex 1 in 14 and to complex I11 in another nine. In each case the data presented were obtained by applying classical biochemical methods to purified mitochondria freshly isolated from a sample of the vastus lateralis muscle taken under light general anaesthesia (Morgan-Hughes et al., 1977). Case 1 was a 21-year-old woman with fatiguable muscle weakness dating back to early childhood. At the age of 11 years she developed unexplained congestive heart failure, which resolved spontaneously after several months. Her subsequent referral was precipitated by the death of a 23-