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Cytochrome C Oxidoreductase Deficiency

Cytochrome C oxidoreductase (COX) deficiency is a rare metabolic disorder. It can be either inherited or acquired by mutation. It results from an inability of mitochondria, the powerhouses of cells, to produce the enzyme, which is also called Complex IV. The deficiency may be localized or exist in all organs.

  1. Frequency

    • The frequency of respiratory chain defects is estimated at 1 in 10,000 newborns and those having to do with Complex IV constitute about one quarter of them. The incidence among French-Canadians is much higher.

    Natural Function

    • COX normally serves as a catalyst in the final step of the respiratory chain in the conversion of food into ATP, the energy currency used in cellular reactions. The process occurs within mitochondria where oxidative respiration (use of oxygen to extract energy from food) occurs.

    Symptoms

    • The lack of COX causes a traffic jam in the ATP-making process. This prevents the mitochondria from producing enough energy for the cells to function properly. Inability of the regular oxidative respiration to function properly forces cells to break down foods anaerobically--by glycolysis--for energy. This not only is less efficient but also leads to a buildup of lactic acid, eventual acidification of the blood, and death. Other symptoms include lack of muscular function, visual degeneration, and brain defects. Liver failure and brain lesions are common causes of death. Because COX deficiency may be localized, it is not necessarily an early death sentence: the NIH reports of a 27-year-old nurse and a 36-year-old woman with the disease, though both have severe exercise aversion due to lactic acid buildup.

    Four Types

    • As there are numerous mutations that can lead to COX deficiency, there are multiple types of COX deficiency---four in all. COX Deficiency Type Benign Infantile Mitochondrial Myopathy is localized to skeletal muscles. COX Deficiency Type Infantile Mitochondrial Myopathy is more general, additionally exhibiting acidic blood, and kidney and heart abnormalities. Leigh's Disease is systemic, affecting the heart, kidneys, liver, muscles, and effecting progressive brain degeneration. COX Deficiency French-Canadian Type affects the brain, liver, muscles, and blood acid level.

    Treatment

    • Dichloroacetate (DCA) has been effected in reducing lactic acid levels and increasing brain metabolic function in sufferers of mitochondrial disorders. This benefit is particularly strong in Complex I deficiency though. Furthermore, brain lesions have disappeared in a Leigh syndrome sufferer upon administration of DCA.

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