Neuropathologic aspects of cytochrome C oxidase deficiency

Cytochrome c oxidase (COX) deficiency is an important cause of myopathy or encephalomyopathy. Considering the structural complexity of COX, its dual genetic control, and the several nuclear genes needed for its proper assembly, the phenotypic heterogeneity is not surprising. From a morphologic view point, the application of histochemistry and immunohistochemistry to the study of COX deficiency in muscle has revealed specific patterns that -we believe- are helpful both for diagnosis and for directing sequencing studies of either mitochondrial DNA (mtDNA) or nuclear DNA (nDNA) genes. Similar studies in brain have shown that patients with mutations in mtDNA appear to have different patterns of COX deficiency from patients with mutations in nDNA genes. The recent discovery of mutations in COX assembly genes coupled with the potential to generate knock-out mice with these mutations holds the promise of providing the neuropathologist with the animal models needed to study the pathogenesis of COX deficiency in brain and muscle.