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

Abstract

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.

Stomachs of Mice Lacking the Gastric H,K-ATPase α-Subunit Have Achlorhydria, Abnormal Parietal Cells, and Ciliated Metaplasia

“…One possibility is that covalent modification of the pump might lead to cell injury (discussed in Ref. 8), as observed in Clara cells of the lung after covalent binding of 4-ipomeanol to cellular proteins (29).…”

Fatal hepatic failure with lactic acidaemia, fanconi syndrome and defective activity of succinate: Cytochromec reductase

“…Some had predominant encephalomyopathy (Behbehani et at., 1984;Fischer et al, 1986), but in others laboratory data confirmed hepatic and renal involvement as well (Sperl et al, 1988;Birch-Machin et al, 1989). In ou r patient the clinical presentation included hypotonia and respiratory distress and the amino acid analysis revealed a Fanconi syndrome, suggesting muscular and renal involvement; however, the preponderance of the hepatic symptoms determined that the patient's condition was first attributed to a metabolic liver disease: tyrosinaemia, galactosaemia or a defect in the gluconeogenesis.…”

mtDNA Disease in the Primary Care Setting

“…[5][6][7] However, owing to heteroplasmy, patients whose defective mitochondria are not concentrated in muscle may not have ragged red fibers. [31][32][33] Muscle biopsy results are thus relatively specific, but not sensitive for mitochondrial disorders.…”