5 - Cytochrome oxidase deficiency: progress and problems

Abstract

This chapter discusses the cytochrome oxidase (COX) deficiencies within the framework of a classification of the mitochondrial encephalomyopathies based on genetic criteria. Although the molecular basis of many forms of COX deficiency is still unknown, the classification presented allows rational pathogenetic mechanisms to be proposed for some COX deficiencies and genetic mechanisms to be postulated for others. As molecular probes are available for each of the 13 subunits of COX, experimental verification of the hypothetical mechanisms should be forthcoming. Thus, defects in nuclear DNA (nDNA) explain both tissue-specific and generalized forms of COX deficiency that are transmitted by mendelian inheritance and do not affect other enzymes of the respiratory chain. However, this hypothesis has not yet been borne out by experimental evidence. The defects in mitochondrial DNA (mtDNA) and defects in intergenomic communication explain the usually incomplete and nonspecific COX deficiencies in syndromes associated with mtDNA deletions or point mutations and mtDNA depletion.