Defects in citric acid cycle and the electron transport chain in progressive poliodystrophy.
We will present 8 children with progressive infantile or juvenile poliodystrophy (Alpers' disease), associated with a defect in pyruvate metabolism. Laboratory studies showed elevated levels of lactate in CSF and, in 4 children, elevated levels in serum. Histopathologic studies revealed lipid storage in liver and/or muscle tissue, sometimes myopathy with abnormal mitochondria and slight axonal degeneration in the peripheral nerve. Autopsy showed the characteristics of progressive poliodystrophy with degeneration and loss of neurons. Electron microscopy of cerebral cortex showed no mitochondrial abnormalities in neurons or astroglia. Biochemical studies in muscle and/or liver and/or cerebral tissue showed different deficiencies in pyruvate metabolism: in the pyruvate dehydrogenase complex, in the second part of the citric acid cycle (after the oxoglutarate dehydrogenase complex), in the NADH oxidation, in cytochrome aa3 and in pyruvate carboxylase.
D000293:Adolescent; D001921:Brain / Q000201:enzymology; D002245:Carbon Dioxide / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D002952:Citric Acid Cycle; D004579:Electron Transport; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D007962:Leukocytes / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D009123:Muscle Hypotonia / Q000201:enzymology; D009128:Muscle Spasticity / Q000201:enzymology; D009245:NADH Dehydrogenase / Q000378:metabolism; D009468:Neuromuscular Diseases / Q000201:enzymology*; D010243:Paralysis / Q000201:enzymology*; D011596:Psychomotor Disorders / Q000201:enzymology*; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid
D007773:Lactates; D011768:Pyruvate Dehydrogenase Complex; D011773:Pyruvates; D002245:Carbon Dioxide; D019344:Lactic Acid; D019289:Pyruvic Acid; D009245:NADH Dehydrogenase