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Cytochrome C Oxidase Deficiency
Condition Overview: Cytochrome C Oxidase Deficiency is a very rare inherited metabolic disorder characterized by deficiency of the enzyme cytochrome C oxidase (COX), or Complex IV, an essential enzyme that is active in the subcellular structures that help to regulate energy production (mitochondria). Deficiency of COX may be limited (localized) to the tissues of the skeletal muscles or may affect several tissues, such as the heart, kidney, liver, brain, and/or connective tissue (fibroblasts); in other cases, the COX deficiency may be generalized (systemic).Four distinct forms of Cytochrome C Oxidase Deficiency have been identifed. The first form of this disorder is known as COX Deficiency Type Benign Infantile Mitochondrial Myopathy. Affected infants exhibit many of the same symptoms as those with the more severe infantile form of the disease; however, because the COX deficiency is limited (localized) to tissues of the skeletal muscles, they typically do not have heart or kidney dysfunction. In the second type of the disease, known as COX Deficiency Type Infantile Mitochondrial Myopathy, because the COX deficiency affects tissues of the skeletal muscles as well as several other tissues, the disorder may be characterized by a generalized weakness of skeletal muscles (myotonia), abnormalities of the heart and kidneys, and/or abnormally high levels of lactic acid in the blood (lactic acidosis). The third form of COX Deficiency, known as Leigh's Disease (Subacute Necrotizing Encephalomyelopathy), is thought to be a generalized (systemic) form of COX Deficiency. Leigh's Disease is characterized by progressive degeneration of the brain and dysfunction of other organs of the body including the heart, kidneys, muscles, and liver. Symptoms may include loss of previously acquired motor skills, loss of appetite, vomiting, irritability, and/or seizure activity. As Leigh's Disease progresses, symptoms may also include generalized weakness; loss of muscle tone (hypotonia); and/or episodes of lactic acidosis. In the fourth form of COX Deficiency, known as COX Deficiency French-Canadian Type, the COX deficiency affects tissues of the skeletal muscles, connective tissue, and, in particular, the brain (Leigh's Disease) and the liver. Affected infants and children may demonstrate developmental delays, diminished muscle tone (hypotonia), crossing of the eyes (strabismus), Leigh's Disease, and/or episodes of lactic acidosis. Many cases of COX Deficiency are inherited as an autosomal recessive genetic trait. However, it is possible that other cases may be inherited due to abnormal changes in genetic material (mutation) found within mitochondria (mtDNA). |
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