Cytochrome-c Oxidase Deficiency

A disease that results from a congenital defect in ELECTRON TRANSPORT COMPLEX IV. Defects in ELECTRON TRANSPORT COMPLEX IV can be caused by mutations in the SURF1, SCO2, COX10, or SCO1 genes. ELECTRON TRANSPORT COMPLEX IV deficiency caused by mutation in SURF1 manifests itself as LEIGH DISEASE; that caused by mutation in SCO2 as fatal infantile cardioencephalomyopathy; that caused by mutation in COX10 as tubulopathy and leukodystrophy; and that caused by mutation in SCO1 as early-onset hepatic failure and neurologic disorder. (from Online Mendelian Inheritance in Man, http://www.ncbi.nlm.nih.gov/Omim, MIM#220110, May 17, 2001)

Also Known As:

Networked: 123 relevant articles (3 outcomes, 12 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Mitochondrial Myopathies (Mitochondrial Myopathy)
2.	Mitochondrial Encephalomyopathies (Mitochondrial Encephalomyopathy)
3.	Glycogen Storage Disease (Glycogenosis)
4.	Motor Neuron Disease (Primary Lateral Sclerosis)
5.	Amyotrophic Lateral Sclerosis (Lou Gehrig's Disease)

Experts

1.	Jacobs, Howard T: 5 articles (01/2015 - 04/2009)
2.	Rustin, Pierre: 4 articles (01/2015 - 04/2009)
3.	Dufour, Eric: 3 articles (01/2015 - 04/2009)
4.	Taylor, Robert W: 3 articles (09/2014 - 03/2009)
5.	Zeviani, Massimo: 3 articles (09/2014 - 03/2002)
6.	Morin, Charles: 3 articles (08/2004 - 01/2003)
7.	Leary, Scot C: 2 articles (06/2015 - 05/2008)
8.	Ohtake, Akira: 2 articles (12/2014 - 03/2010)
9.	Murayama, Kei: 2 articles (12/2014 - 03/2010)
10.	Kemppainen, Kia K: 2 articles (10/2014 - 04/2014)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Cytochrome-c Oxidase Deficiency:

1.	Electron Transport Complex IV (Cytochrome c Oxidase)IBA 10/01/1988 - "Immunocytochemical studies of cytochrome oxidase subunits in skeletal muscle of patients with partial cytochrome oxidase deficiencies." 03/01/2010 - "Mutations in the SCO2 gene [SCO cytochrome oxidase deficient homolog 2 (yeast)] causing cytochrome c oxidase deficiency have been reported in at least in 26 patients with fatal infantile cardioencephalomyopathy. " 08/15/2003 - "We have characterized the respiration-deficient cox17 mutants and found in addition to the expected cytochrome oxidase deficiency, a specific lack of Cox2p and the presence of a misassembled cytochrome oxidase in a subset of mutants. " 11/01/2002 - "The lengths of the cytochrome c oxidase-negative segments were generally shorter in the less severely affected biopsy, and we frequently observed non-contiguous segments of cytochrome c oxidase deficiency within the same muscle fibre. " 08/01/2001 - "The measured catalytic activity of cytochrome c oxidase in skeletal muscle homogenates demonstrated a partial cytochrome c oxidase deficiency No abnormalities in the mitochondrial genome and in the SURF-1 gene were found. "
2.	DNA (Deoxyribonucleic Acid)IBA 03/05/2006 - "SURF1 mutations associated with cytochrome c oxidase deficiency were identified in 8 (12.3%) families by DNA sequencing. " 11/01/1995 - "Nuclear DNA origin of cytochrome c oxidase deficiency in Leigh's syndrome: genetic evidence based on patient's-derived rho degrees transformants." 05/01/1989 - "Cytochrome c oxidase deficiency in Leigh's syndrome: genetic evidence for a nuclear DNA-encoded mutation." 04/01/2005 - "Cytochrome oxidase deficiency protects Escherichia coli from cell death but not from filamentation due to thymine deficiency or DNA polymerase inactivation." 03/01/2010 - "Administration of sodium pyruvate may prove effective for other patients with cytochrome c oxidase deficiency due to mitochondrial or nuclear DNA mutations."
3.	alternative oxidaseIBA 04/15/2014 - "Expression of alternative oxidase in Drosophila ameliorates diverse phenotypes due to cytochrome oxidase deficiency." 01/01/2015 - "Diiron centre mutations in Ciona intestinalis alternative oxidase abolish enzymatic activity and prevent rescue of cytochrome oxidase deficiency in flies." 10/01/2014 - "Transgenic expression in Drosophila of the alternative oxidase (AOX) derived from Ciona intestinalis has previously been shown to mitigate the toxicity of respiratory chain inhibitors and to rescue mutant and knockdown phenotypes associated with cytochrome oxidase deficiency. " 12/01/2009 - "The alternative oxidase, a tool for compensating cytochrome c oxidase deficiency in human cells." 04/01/2009 - "Expression of the alternative oxidase complements cytochrome c oxidase deficiency in human cells."
4.	Pyruvic Acid (Pyruvate)IBA 03/01/2010 - "These data indicate that pyruvate therapy was effective in improving exercise intolerance at least in a patient with cytochrome c oxidase deficiency. " 03/01/2010 - "Pyruvate therapy for Leigh syndrome due to cytochrome c oxidase deficiency." 02/01/1989 - "Stable-isotope tracer experiments performed in vitro are evaluated for their utility in differentiating between pyruvate dehydrogenase and cytochrome oxidase deficiencies, two of several enzyme defects commonly associated with the lactic acidemias. " 03/01/2010 - "In an attempt to circumvent the mitochondrial dysfunction, we orally applied sodium pyruvate and analyzed its effect on an 11-year-old female with Leigh syndrome due to cytochrome c oxidase deficiency accompanied by cardiomyopathy. " 03/01/2010 - "Administration of sodium pyruvate may prove effective for other patients with cytochrome c oxidase deficiency due to mitochondrial or nuclear DNA mutations."
5.	Zidovudine (Retrovir)FDA LinkGeneric 10/01/1993 - "Among zidovudine receivers, cytochrome c oxidase deficiency was found in 10 of 10 patients from Group 1 and 7 of 10 from Group 2. No cytochrome c oxidase deficiency was observed in patients not treated by zidovudine. " 12/01/1995 - "Cytochrome c oxidase deficiency in zidovudine myopathy affects perifascicular muscle fibres and arterial smooth muscle cells." 10/01/1993 - "Zidovudine can induce a mitochondrial myopathy with ragged-red fibers and partial cytochrome c oxidase deficiency. " 01/01/1993 - "Tubular aggregates and partial cytochrome c oxidase deficiency in skeletal muscle of patients with AIDS treated with zidovudine." 10/01/1993 - "When present, cytochrome c oxidase-negative fibers accounted for 2 to 28% of fibers, and there was no difference for the number of cytochrome c oxidase-negative fibers between Group 1 and Group 2. Most patients with cytochrome c oxidase deficiency that could be evaluated clinically after muscle biopsy improved after withdrawal of zidovudine (5 of 7 in Group 1, 5 of 5 in Group 2). "
6.	SodiumIBA 03/01/2010 - "In an attempt to circumvent the mitochondrial dysfunction, we orally applied sodium pyruvate and analyzed its effect on an 11-year-old female with Leigh syndrome due to cytochrome c oxidase deficiency accompanied by cardiomyopathy. " 03/01/2010 - "Administration of sodium pyruvate may prove effective for other patients with cytochrome c oxidase deficiency due to mitochondrial or nuclear DNA mutations."
7.	CopperIBA 04/01/1965 - "CYTOCHROME OXIDASE DEFICIENCY IN THE MOTOR NEURONES OF COPPER-DEFICIENT LAMBS: A HISTOCHEMICAL STUDY." 06/02/2015 - "Our analyses define COA6 as a constituent of the mitochondrial copper relay system, linking defects in COX2 metallation to cardiac cytochrome c oxidase deficiency. " 02/01/2006 - "Cardiac cytochrome-c oxidase deficiency occurs during late postnatal development in progeny of copper-deficient rats." 04/01/1999 - "Biochemical micromethods were used for the investigation of changes in mitochondrial oxidative phosphorylation associated with cytochrome c oxidase deficiency in brain cortex from Mo(vbr) (mottled viable brindled) mice, an animal model of Menkes' copper deficiency syndrome. " 04/01/1999 - "Metabolic consequences of the cytochrome c oxidase deficiency in brain of copper-deficient Mo(vbr) mice."
8.	Mitochondrial DNA (mtDNA)IBA 08/01/2010 - "OPA1 mutations cause cytochrome c oxidase deficiency due to loss of wild-type mtDNA molecules." 11/01/2002 - "Skeletal muscle shows mitochondrial abnormalities, including ragged-red fibers and cytochrome c oxidase deficiency, together with mtDNA depletion, multiple deletions or both. " 04/25/2000 - "A new mtDNA mutation associated with a progressive encephalopathy and cytochrome c oxidase deficiency." 04/01/1997 - "A significant number of cytochrome c oxidase deficiencies, often associated with other respiratory chain enzyme defects, are attributed to mutations of mtDNA. " 12/01/1996 - "Muscle biopsy samples of advanced cases showed ragged-red fibers, focal cytochrome c oxidase deficiency, and multiple mtDNA deletions by Southern blot analysis. "
9.	Lactic AcidFDA LinkGeneric 03/01/1998 - "Diagnostic studies revealed an elevated protein and lactate in the cerebrospinal fluid, slow-wave and intermittently continuous spike-wave activity in the EEG, and a complex i.v. (cytochrome-C oxidase) deficiency in the muscle biopsy. " 06/04/1994 - "Since she had slightly elevated lactate in the cerebrospinal fluid, a muscle biopsy was done which revealed scattered ragged-red fibres and focal cytochrome c oxidase deficiency. " 12/01/2013 - "Leigh syndrome is a mitochondrial encephalomyopathy that occurs due to "cytochrome c oxidase deficiency" characterized by psychomotor retardation, difficulty in eating, seizures, hypotonia, respiratory disorders and high lactate levels. " 12/01/2014 - "We report on a further patient, first child of healthy consanguineous parents, with severe developmental delay, seizures, hyperintensities of the basal ganglia on magnetic resonance imaging (MRI), progressive brain atrophy, optic nerve atrophy, repeatedly elevated blood lactate, and respiratory chain complexes I, I + III and cytochrome c oxidase deficiencies with borderline depletion of mitochondrial DNA in muscle tissue. " 09/01/1989 - "We investigated the time course of the formation of lactate and pyruvate from glucose in cultured skin fibroblasts from controls, from a patient with a cytochrome c oxidase deficiency and from controls treated with inhibitors of the individual respiratory chain complexes. "
10.	OxidoreductasesIBA 02/01/1989 - "Stable-isotope tracer experiments performed in vitro are evaluated for their utility in differentiating between pyruvate dehydrogenase and cytochrome oxidase deficiencies, two of several enzyme defects commonly associated with the lactic acidemias. " 01/01/1993 - "To confirm the specificity of these studies in differentiating primary from secondary carnitine deficiency disorders, we have studied carnitine uptake in the cultured skin fibroblasts from 5 children who have various enzymatic defects in intramitochondrial beta-oxidation including short-chain, medium-chain and long-chain acyl-CoA dehydrogenase and short-chain L-3-hydroxyacyl-CoA dehydrogenase deficiencies, and in 4 children with cytochrome oxidase deficiency. " 01/01/1994 - "In fibroblasts from patients with complex IV (cytochrome c oxidase) deficiency or glutaricaciduria type II, phytanic acid alpha-oxidation was reduced to 14% of normal, whereas in myoblasts from patients with complex I (NADH-Q reductase) deficiency, it was normal. " 10/01/1992 - "We found that cells from patients with most forms of cytochrome oxidase deficiency, cells with complex I deficiency, cells with multiple respiratory chain defects and cells with severe pyruvate dehydrogenase (PDH) complex deficiency failed to survive when subcultured into galactose (5 mM) medium. " 04/01/1999 - "Disorders of glycogen, lipid, or mitochondrial metabolism may cause three main clinical syndromes in muscle, namely, (1) progressive weakness with hypotonia (e.g., acid maltase, debrancher enzyme, and brancher enzyme deficiencies among the glycogenoses; carnitine uptake and carnitine acylcarnitine translocase defects among the fatty acid oxidation (FAO) defects; and cytochrome oxidase deficiency among the mitochondrial disorders) or (2) acute, recurrent, reversible muscle dysfunction with exercise intolerance and acute muscle breakdown or myoglobinuria (with or without cramps), e.g., phosphorylase, phosphofructokinase, and phosphoglycerate kinase among the glycogenoses and carnitine palmitoyltransferase II deficiency among the disorders of FAO or (3) both (e.g., long-chain or very long-chain acyl coenzyme A (CoA) dehydrogenase, short-chain L-3-hydroxyacyl-CoA dehydrogenase, and trifunctional protein deficiencies among the FAO defects). "

Therapies and Procedures

1.	Heart Transplantation (Grafting, Heart) 02/01/2003 - "Eleven patients with cardiomyopathy died, including all eight with cytochrome-c oxidase deficiency, and one patient underwent a heart transplantation. "
2.	Denervation 02/01/2004 - "Atrophied fibers often demonstrated no subsarcolemmal mitochondrial staining, suggesting denervation, whereas hypertrophied fibers often demonstrated cytochrome oxidase deficiency, suggesting mitochondrial dysfunction. "