Myopathy and Fatal Cardiopathy due to Cytochrome c Oxidase Deficiency

A 3-day-old girl had a syndrome of lethargy and lactic acidosis. Pregnancy and delivery had been normal; there was no consanguinity or family history of neuromuscular disease. At age 41/2 months, she had generalized weakness, hypotonia, areflexia, and macroglossia. She developed cyanosis and respiratory failure, and marked cardiomegaly was noted. She died at age 81/2 months of cardiac arrest. Results from a muscle biopsy specimen obtained at age 41/2 months showed ragged-red fibers and increased glycogen and lipid droplets. With the cytochrome c oxidase reaction, only 5% of the fibers stained positively in the biopsy specimen. Cytochrome c oxidase activity was 7.3% of normal in muscle mitochondria and 12.2% of normal in heart mitochondria. Reduced-minus-oxidized cytochrome spectra showed lack of the cytochrome aa₃ peak. Immunotitration using antibodies against purified human heart cytochrome c oxidase showed normal amount of cross-reacting material in both heart and muscle. The genetic error could have involved a cytochrome c oxidase isozyme common to heart and muscle.