GTR Home > Conditions/Phenotypes > Cytochrome-c oxidase deficiency


Complex IV (cytochrome c oxidase; EC is the terminal enzyme of the respiratory chain and consists of 13 polypeptide subunits, 3 of which are encoded by mitochondrial DNA. The 3 mitochondrially encoded proteins in the cytochrome oxidase complex are the actual catalytic subunits that carry out the electron transport function (Saraste, 1983). See 123995 for discussion of some of the nuclear-encoded subunits. Shoubridge (2001) provided a comprehensive review of cytochrome c oxidase deficiency and noted that most isolated COX deficiencies are inherited as autosomal recessive disorders caused by mutations in nuclear-encoded genes; mutations in the mtDNA-encoded COX subunit genes are relatively rare. [from OMIM]

Associated genes

Clinical features

  • Glycosuria
  • Proteinuria
  • Anemia
  • Increased CSF lactate
  • Respiratory insufficiency due to muscle weakness
  • Increased serum lactate
  • Intellectual disability
  • Lactic acidosis
  • Renal Fanconi syndrome
  • Seizure
  • Failure to thrive
  • Renal tubular dysfunction
  • Sensorineural hearing impairment
  • Ptosis
  • Pigmentary retinopathy
  • Optic atrophy
  • Ataxia
  • Muscular hypotonia
  • Global developmental delay
  • Motor delay
  • Decreased liver function
  • Hypertrophic cardiomyopathy
  • Hepatomegaly
  • Exertional dyspnea
  • Respiratory difficulties
  • Hyperphosphaturia
  • Aminoaciduria
  • Exercise intolerance
  • Decreased activity of cytochrome C oxidase in muscle tissue
  • Increased hepatocellular lipid droplets
  • Increased intramyocellular lipid droplets
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