Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085584 (encephalopathy)
 18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytochrome c oxidase (COX) is the terminal enzyme of the mitochondrial respiratory chain, catalyzing the transfer of electrons from reduced cytochrome c to molecular oxygen. It is composed of 13 structural subunits, three of which are encoded in mtDNA and form the catalytic core of the enzyme. In addition to these structural subunits, a large number of accessory factors are necessary for the assembly and maintenance of the active holoenzyme complex. Most isolated COX deficiencies are inherited as autosomal recessive disorders; mutations in the mtDNA-encoded COX subunit genes are relatively rare. These mutations are associated with a wide spectrum of clinical phenotypes ranging from isolated myopathy to multisystem disease, with onset from late childhood to adulthood. Autosomal recessive COX deficiencies generally have a very early age of onset and a fatal outcome. Several clinical presentations have been described including Leigh Syndrome, hypertrophic cardiomyopathy and myopathy, and fatal infantile lactic acidosis. Surprisingly, mutations in the nuclear-encoded structural COX subunits have not been found in association with any of these phenotypes. Mutations have, however, been identified in several COX assembly factors: SURF1 (Leigh Syndrome), SCO2 (hypertrophic cardiomyopathy), SCO1 (hepatic failure, ketoacidotic coma), and COX10 (encephalopathy, tubulopathy). As all of these assembly factors are ubiquitously expressed, the molecular basis for the different clinical presentations remains unexplained. Although the genetic defects in the majority of patients with COX deficiency are unknown, it is likely that most will be solved in the near future using functional complementation techniques.
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PMID:Cytochrome c oxidase deficiency. 1157 24

Cytochrome c oxidase (COX) deficiency has been associated with a wide spectrum of clinical features and may be caused by mutations in different genes of both the mitochondrial and the nuclear DNA. In an attempt to correlate the clinical phenotype with the genotype in 16 childhood cases, mtDNA was analysed for deletion, depletion, and mutations in the three genes encoding COX subunits and the 22 tRNA genes. Furthermore, nuclear DNA was analysed for mutations in the SURF1, SCO2, COX10, and COX17 genes and cases with mtDNA depletion were analysed for mutations in the TK2 gene. SURF1-mutations were identified in three out of four cases with Leigh syndrome while a mutation in the mitochondrial tRNA (trp) gene was identified in the fourth. One case with mtDNA depletion had mutations in the TK2 gene. In two cases with leukoencephalopathy, one case with encephalopathy, five cases with fatal infantile myopathy and cardiomyopathy, two cases with benign infantile myopathy, and one case with mtDNA depletion, no mutations were identified. We conclude that COX deficiency in childhood should be suspected in a wide range of clinical settings and although an increasing number of genetic defects have been identified, the underlying mutations remain unclear in the majority of the cases.
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PMID:Genotypes and clinical phenotypes in children with cytochrome-c oxidase deficiency. 1468 57