Cytochrome c oxidase deficiency

Cytochrome c oxidase (COX) is the terminal enzyme of the mitochondrial resp iratory chain, catalyzing the transfer of electrons from reduced cytochrome c to molecular oxygen. It is composed of 13 structural subunits, three of which are encoded in mtDNA and form the catalytic core of the enzyme. In ad dition to these structural subunits, a large number of accessory factors ar e necessary for the assembly and maintenance of the active holoenzyme compl ex. Most isolated COX deficiencies are inherited as autosomal recessive dis orders; mutations in the mtDNA-encoded COX subunit genes are relatively rar e. These mutations are associated with a wide spectrum of clinical phenotyp es ranging from isolated myopathy to multisystem disease, with onset from l ate childhood to adulthood. Autosomal recessive COX deficiencies generally have a very early age of onset and a fatal outcome. Several clinical presen tations have been described including Leigh Syndrome, hypertrophic cardiomy opathy and myopathy, and fatal infantile lactic acidosis. Surprisingly, mut ations in the nuclear-encoded structural COX subunits have not been found i n association with any of these phenotypes. Mutations have, however, been i dentified in several COX assembly factors: SURF1 neigh Syndrome), SCO2 (hyp ertrophic cardiomyopathy), SCO I (hepatic failure, ketoacidotic coma), and COX IO(encephalopathy, tubulopathy). As all of these assembly factors are u biquitously expressed, the molecular basis for the different clinical prese ntations remains unexplained. Although the genetic defects in the majority of patients with COX deficiency are unknown, it is likely that most will be solved in the near future using functional complementation techniques. (C) 2001 Wiley-Liss, Inc.