Findings in muscle in complex I (NADH coenzyme Q reductase) deficiency.

Thirteen of 15 patients with complex I deficiency had the multisystemic form, with strokelike episodes and other symptoms that fulfilled the diagnostic requirements for MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes), and 2 had only muscle fatigability and weakness, having the purely myopathic form. In the multisystemic form, 12 patients had ragged-red fibers. All multisystemic patients had myopathic histochemical abnormalities that consisted of mild to moderate variation in fiber size, disorganized intermyofibrillar networks, type 2 fiber atrophy, and an increased number of type 2C fibers. Five of 13 multisystemic patients had decreased cytochrome c oxidase (CCO) activity in extrafusal fibers, with sparing of intrafusal muscle fibers. In the myopathic form, pathological findings were similar to those in the multisystemic form. In addition to complex I and NADH dehydrogenase activities being decreased, the CCO activity was significantly decreased (less than 50% of control value) in 8 patients, especially when the disease was in its advanced stages, suggesting that CCO enzyme might be secondarily affected as the disease progresses.