MUSCLE CYTOCHROME-C-OXIDASE DEFICIENCY ACCOMPANIED BY A URINARY ORGANIC-ACID PATTERN MIMICKING MULTIPLE ACYL-COA DEHYDROGENASE-DEFICIENCY

Cytochrome c oxidase (COX, EC 1.9.3-1) is part of the electron-transfer chain, where it is known as comlex IV. COX is composed of 13 different subunits: 3 are encoded by mitochondrial DNA while 10 are coded for by nuclear DNA. Given this complexity, it is not surprising that COX deficiency can cause diseases with many different clinical entities: from isolated muscle symptoms (Dimauro et al 1990) to severe progressive neurodegenerative diseases ending with death usually before the second year of life (e.g. Leigh syndrome) (Arts et al 1987). Some cases of COX deficiency have a generalized defect of this enzyme, while others have a defect restricted to one or a limited number of tissues (e.g. skeletal muscles alone). Most reported cases of COX deficiency have been accompanied by lactic acidaemia and/or elevated urinary excretion of lactic acid. However, other organic acid patterns have not been described in isolated COX deficiency. In this communicaton, we describe a patient with muscle COX deficiency and an organic acid pattern in urine similar to that found in multiple acyl-CoA dehydrogenase (MAD) deficiency. In MAD deficiency, the oxidation rate of [9,10(n)-H-3]myristic acid is very much decreased owing to a defect in electron-transfer flavoprotein (ETF) or its dehydrogenase (ETF-DH). Our patient had a normal rate of [9,10(n)-H-3] myristic acid oxidation in fibroblasts.