Human Complex I deficiency: Clinical spectrum and involvement of oxygen free radicals in the pathogenicity of the defect

Human NADH-ubiquinione oxidoreductase deficiency can be present in a wide variety of biochemical and symptomatic phenotypes. In fact, the observed spectrum of severity varies from fatal infantile lactic acidosis to adult onset exercise intolerance or optic neuropathy. Since most genetic diseases display a much more narrow set of indices, perhaps this wide variety of clinical presentation requires some explanation. Many of the problems that revolve around the diagnosis of Complex I defects stem from the fact that Complex I is a huge multienzyme complex of 41 separately encoded gene products derived from both w x nuclear and mitochondrial genomes 1,2 . This dual coding system leads to a number of difficulties, misconceptions and pitfalls surrounding etiology and diagnosis. In addition, a further complicating factor related to oxygen free radical generation seems to be an important factor in the determination of pathology in affected individuals.