NADH COENZYME-Q REDUCTASE (COMPLEX-I) DEFICIENCY - HETEROGENEITY IN PHENOTYPE AND BIOCHEMICAL FINDINGS

Twelve patient cell lines with biochemically proven complex I deficien cy were compared for clinical presentation and outcome, together with their sensitivity to galactose and menadione toxicity. Each patient ha d elevated lactate to pyruvate ratios demonstrable in fibroblast cultu res. Each patient also had decreased rotenone-sensitive NADH-cytochrom e c reductase (complexes I and III) with normal succinate cytochrome c reductase (complexes II and III) and cytochrome oxidase (complex IV) activity in cultured skin fibroblasts, indicating a deficient NADH-coe nzyme Q reductase (complex I) activity. The patients fell into five ca tegories: severe neonatal lactic acidosis; Leigh disease; cardiomyopat hy and cataracts; hepatopathy and tubulopathy; and mild symptoms with lactic acidaemia. Cell lines from 4 out of the 12 patients were suscep tible to both galactose and menadione toxicity and 3 of these also dis played low levels of ATP synthesis in digitonin-permeabilized skin fib roblasts from a number of substrates. This study highlights the hetero geneity of complex I deficiency at the clinical and biochemical level.