Mitochondrial cytochrome deficiency presenting as a myopathy with hypotonia, external ophthalmoplegia, and lactic acidosis in an infant and as fatal hepatopathy in a second cousin

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Abstract
Fatal infantile mitochondrial myopathy with lactic acidosis, morphologically abnormal mitochondria, deficient cytochromes aa3 and b, and a Fanconi-like aminoaciduria was described. Two infants, 2nd cousins, are reported with a similar fatal mitochondrial disorder, the cytochrome deficiency limited to skeletal muscle in 1 child and to liver in the other. The 1st child at 3 mo. of age had weight loss, hypotonia, external ophthalmoplegia and a severe lactic acidosis with a high lactate/pyruvate ratio. EM of muscle showed marked proliferation of enlarged mitochondria, many containing concentric rings of cristae. In skeletal muscle mitochondria, cytochromes aa3 and b were not detectable but cytochrome cc was found to be normal by spectroscopy. Cytochrome c oxidase activity was less than 1% of normal. Mitochondria from kidney, liver, heart, lung and brain examined postmortem had normal cytochromes and preserved cytochrome c oxidase activity. The 2nd cousin at 5 mo. of age had weight loss and hepatomegaly but no systemic lactic acidosis. Liver biopsy showed hepatocytes packed with enlarged mitochondria. The liver mitochondria showed deficiency cytochromes aa3 and b postmortem, and cytochrome c oxidase activity was less than 10% of normal. Kidney mitochondria had normal cytochromes. Muscle was not studied. The mitochondrial abnormality in the 2 cousins presumably is related. Unexplained are the mode of genetic transmissions or environmental exposure and the apparent involvement of a single different organ in each child.