Cytochrome c oxidase deficiency

There are currently 4 known forms of COX deficiency. The range and severity of signs and symptoms can vary widely from case to case.

In one form, referred to as the benign infantile mitochondrial myopathy type, symptoms may be limited to the skeletal muscles. Episodes of lactic acidosis may occur and can cause life-threatening complications if left untreated. However, with appropriate treatment, individuals with this form of the condition may spontaneously recover within the first few years of life.^[1]

In the second form of the disorder, referred to as the infantile mitochondrial myopathy type, the skeletal muscles as well as several other tissues (such as the heart, kidney, liver, brain, and/or connective tissue) are affected. Symptoms associated with this form typically begin within the first few weeks of life and may include muscle weakness; heart problems; kidney dysfunction; failure to thrive; difficulties sucking, swallowing, and/or breathing; and/or hypotonia. Affected infants may also have episodes of lactic acidosis.^[1]

The third form of COX deficiency is thought to be a systemic form of the condition and is referred to as Leigh's disease. This form is characterized by progressive degeneration of the brain as well as dysfunction of several other organs including the heart, kidneys, muscles, and/or liver. Symptoms of this form, which predominantly involve the central nervous system, may begin between three months and two years of age and may include loss of previously acquired motor skills and/or head control; poor sucking ability; loss of appetite; vomiting; irritability; and possible seizures. Intellectual disability may also occur.^[1]

In the fourth form of COX deficiency, the French-Canadian type, the brain (as in Leigh's disease) and liver are particularly affected in addition to the skeletal muscles and connective tissues. However, in this form, the kidneys and heart appear to have near-normal enzyme activity. Individuals with this form may have developmental delay; hypotonia; slight facial abnormalities; Leigh's disease; strabismus; ataxia; liver degeneration; and/or episodes of lactic acidosis.^[1]

Although some mildly affected individuals survive into adolescence or adulthood, this condition is often fatal in childhood.^[2]

There is currently no cure for cytochrome C oxidase (COX) deficiency. Management of all forms of COX deficiency generally focuses on the specific symptoms present in the affected individual and is largely supportive. The goals of treatment are to improve symptoms and slow progression of the disease; the effectiveness of treatment varies with each individual.^[3][4] Treatment generally does not reverse any damage that has already occurred.^[3] Prognosis varies depending on the form of COX deficiency present.^[4] Individuals with benign infantile mitochondrial myopathy may experience spontaneous recovery (although early diagnosis and intensive treatment is still needed until this point), while there may be rapid demise in individuals with Leigh syndrome.^[4]

It is often recommended that individuals with mitochondrial disorders such as COX deficiency avoid fasting. Dehydration due to vomiting or illness may be treated with intravenous fluid if the individual is not able to take fluids orally. Seizures are typically controlled with anticonvulsants. Some affected individuals may benefit from physical, occupational, and speech therapies that are specifically tailored to their needs.^[3] Dietary supplements including certain vitamins and cofactors have shown varying degrees of benefit in individual cases.^[4]

Individuals interested in specific management recommendations for themselves or relatives should speak with their healthcare providers.

There are varying degrees of severity in COX deficiency. Individuals with more severe cases may die during infancy, while those with less severe cases have lived into adulthood.^[5] We cannot predict the life expectancy for a particular child.