6533b85ffe1ef96bd12c1151

RESEARCH PRODUCT

Mitochondrial myopathy with lactic acidosis and deficient activity of muscle succinate cytochrome-c-oxidoreductase

subject

description

A male infant had severe muscular hypotonia from birth. Recurrent vomiting with dehydration and severe metabolic acidosis complicated the course. Elevated lactate (up to 12.3 mmol/l; n less than 2), pyruvate (0.4 mmol/l; n less than 0.05) and alanine levels were found in serum with an abnormal lactate/pyruvate ratio (greater than 30; n less than 15). In urine the concentrations of lactate, pyruvate, alanine and of several intermediates of the citric acid cycle were increased. In muscle, numerous disseminated "ragged red fibres" were found by light microscopy; muscle fibres were found to contain subsarcolemmal aggregates of mitochondria, lipid droplets and glycogen by electromicroscopical methods. Moreover, mitochondria with a typical circular arrangement of cristae were noticed. In liver homogenates normal activities of pyruvate carboxylase and pyruvate dehydrogenase complex were found; in liver mitochondria also succinate-cytochrome-c-oxidoreductase activity was normal. However, in muscle no succinate-cytochrome-c-oxidoreductase activity was detectable. The patient became increasingly lethargic and died because of sepsis at 5 months of age.