The length of cytochrome c oxidase-negative segments in muscle fibres in patients with mtDNA myopathy

Heteroplasmic mitochondrial DNA mutations often cause a skeletal myopathy associated with a mosaic distribution of cytochrome c oxidase-deficient muscle fibres. The function of an individual muscle fibre is dependent upon the metabolic activity throughout its length, but little is known about the length of cytochrome c oxidase-deficient segments in human skeletal muscle in patients with mitochondrial disease. We studied cytochrome c oxidase activity by serial section analysis of quadriceps muscle from two patients. We observed a striking variation in the length of the cytochrome c oxidase-negative segments. The shortest segments were 10 mum long, and the longest segment was the entire length of the larger biopsy (greater than or equal to1.2 mm). The lengths of the cytochrome c oxidase-negative segments were generally shorter in the less severely affected biopsy, and we frequently observed non-contiguous segments of cytochrome c oxidase deficiency within the same muscle fibre. The findings have important implications for our understanding of the pathogenesis and progression of mitochondrial DNA myopathy. (C) 2002 Published by Elsevier Science B.V.