NADH-coenzyme Q reductase (complex I) deficiency: heterogeneity in phenotype and biochemical findings

Journal of Inherited Metabolic Disease - Tập 19 - Trang 675-686 - 1996
S. Pitkanen1, A. Feigenbaum1, R. Laframboise2, B. H. Robinson1
1Departments of Pediatrics and Biochemistry, University of Toronto and The Research Institute, Hospital for Sick Children, Toronto
2Médecine Génétique, Le Centre Hospitalier de L'Université Laval, Ste-Foy, Canada

Tóm tắt

Twelve patient cell lines with biochemically proven complex I deficiency were compared for clinical presentation and outcome, together with their sensitivity to galactose and menadione toxicity. Each patient had elevated lactate to pyruvate ratios demonstrable in fibroblast cultures. Each patient also had decreased rotenone-sensitive NADH-cytochromec reductase (complexes I and III) with normal succinate cytochromec reductase (complexes II and III) and cytochrome oxidase (complex IV) activity in cultured skin fibroblasts, indicating a deficient NADH-coenzyme Q reductase (complex I) activity. The patients fell into five categories: severe neonatal lactic acidosis; Leigh disease; cardiomyopathy and cataracts; hepatopathy and tubulopathy; and mild symptoms with lactic acidaemia. Cell lines from 4 out of the 12 patients were susceptible to both galactose and menadione toxicity and 3 of these also displayed low levels of ATP synthesis in digitonin-permeabilized skin fibroblasts from a number of substrates. This study highlights the heterogeneity of complex I deficiency at the clinical and biochemical level.

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Thông tin xuất bản

Journal of Inherited Metabolic Disease

Tập 19

675-686

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