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:

Complex IV Deficiency; Cox Deficiency; Cytochrome C Oxidase Deficiency; Cytochrome Oxidase Deficiency; Deficiency, Cytochrome-c Oxidase; Mitochondrial Complex IV Deficiency; Complex IV Deficiencies; Cox Deficiencies; Cytochrome Oxidase Deficiencies; Cytochrome-c Oxidase Deficiencies; Deficiencies, Complex IV; Deficiencies, Cox; Deficiencies, Cytochrome Oxidase; Deficiencies, Cytochrome-c Oxidase; Deficiency, Complex IV; Deficiency, Cox; Deficiency, Cytochrome Oxidase; Deficiency, Cytochrome c Oxidase; Oxidase Deficiencies, Cytochrome; Oxidase Deficiencies, Cytochrome-c; Oxidase Deficiency, Cytochrome; Oxidase Deficiency, Cytochrome-c

Networked: 391 relevant articles (7 outcomes, 34 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Mitochondrial Diseases (Mitochondrial Disease)
2.	Mitochondrial Myopathies (Mitochondrial Myopathy)
3.	Mitochondrial Encephalomyopathies (Mitochondrial Encephalomyopathy)
4.	Leigh Disease (Leigh's Disease)
5.	Muscular Diseases (Myopathy)

Experts

1.	Taylor, Robert W: 16 articles (06/2019 - 06/2006)
2.	Zeviani, Massimo: 15 articles (01/2022 - 03/2002)
3.	He, Langping: 9 articles (01/2018 - 03/2009)
4.	Moggio, Maurizio: 9 articles (01/2018 - 01/2009)
5.	Blakely, Emma L: 8 articles (06/2019 - 03/2009)
6.	Leary, Scot C: 8 articles (01/2018 - 03/2002)
7.	Schon, Eric A: 8 articles (01/2018 - 12/2004)
8.	Horvath, Rita: 7 articles (01/2022 - 10/2003)
9.	Bordoni, Andreina: 7 articles (01/2018 - 01/2009)
10.	Corti, Stefania: 7 articles (01/2018 - 01/2009)

Drugs and Biologics

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

1.	Electron Transport Complex IV (Cytochrome c Oxidase)IBA 01/01/2008 - "Structural and histochemical studies carried out in a series of seven cases (from five families) with isolated cytochrome c oxidase (COX) deficiency caused by mutations in the SCO2 gene (1, 2) disclosed changes concentrated in the nervous system, skeletal muscle and myocardium. " 10/01/1988 - "Immunocytochemical studies of cytochrome oxidase subunits in skeletal muscle of patients with partial cytochrome oxidase deficiencies." 04/05/2019 - "In MM muscles, most p-S6 positive fibers showed cytochrome C oxidase (COX) deficiency (U = 5.000, P = 0.001). " 01/01/2019 - "Cytochrome c oxidase (COX) deficiency is a major mitochondrial respiratory chain defect that has vast genetic and phenotypic heterogeneity. " 11/01/2018 - "A recent article in The Journal of Pathology described a novel histochemical technique - nitro blue tetrazolium exclusion assay (NBTx) - to quantify mitochondrial cytochrome c oxidase (COX, or complex IV) deficiency. "
2.	Mitochondrial DNA (mtDNA)IBA 12/01/2005 - "Our report of two patients with isolated COX deficiency and new mutations in COX subunit genes may help to draw more attention to this type of mtDNA defects and provide new aspects for counselling affected families." 07/01/2000 - "Similar studies in brain have shown that patients with mutations in mtDNA appear to have different patterns of COX deficiency from patients with mutations in nDNA genes. " 01/01/2024 - "Mitochondrial DNA analysis revealed an undescribed variant: m.8091G>A in the MT-CO2 gene, associated with a complex IV deficiency and a decrease of the mitochondrial respiratory chain capabilities. " 11/01/2023 - "All patients displayed mitochondrial changes in muscle including cytochrome c oxidase deficiency and the mitochondrial DNA mutation load was high. " 12/01/2021 - "Single mitochondrial DNA deletion and isolated complex IV deficiency were noted. "
3.	DNA (Deoxyribonucleic Acid)IBA 09/01/2012 - "COX deficiency is well described as a marker of mitochondrial (mt) DNA dysfunction. " 03/05/2006 - "SURF1 mutations associated with cytochrome c oxidase deficiency were identified in 8 (12.3%) families by DNA sequencing. " 01/01/2006 - "Marked prevalence of two nuclear DNA mutations (845-846delCT in the SURF1 gene and 1541G>A in the SCO2 gene) associated with COX deficiency in a Slavonic population suggests the existence of regional differences in the genetic basis of COX deficiency." 11/01/1998 - "DNA from one patient with severe COX deficiency and with consanguineous parents was entirely sequenced. " 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."
4.	Monoclonal AntibodiesIBA 01/01/1995 - "In the present study a new monoclonal antibody, which reacts exclusively with heart-type human COX subunit VIIa (VIIa-H), and other monoclonal antibodies against human COX subunits, were used in the immunohistochemical analysis of skeletal muscle from children with different forms of mitochondrial myopathy with COX deficiency. " 05/11/2001 - "We show that quantitative measurements of steady-state levels of subunits by monoclonal antibody reactivity, when used in combination with a discontinuous sucrose gradient methods, provide an improved diagnosis of COX deficiencies by distinguishing between kinetic, stability, and assembly defects. "
5.	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." 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." 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. "
6.	alternative oxidaseIBA 04/15/2014 - "Expression of alternative oxidase in Drosophila ameliorates diverse phenotypes due to cytochrome oxidase deficiency." 12/17/2015 - "Diiron centre mutations in Ciona intestinalis alternative oxidase abolish enzymatic activity and prevent rescue of cytochrome oxidase deficiency in flies." 08/21/2014 - "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."
7.	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." 01/01/1991 - "Partial cytochrome c oxidase deficiency and cytoplasmic bodies in patients with zidovudine myopathy."
8.	Sucrose (Saccharose)IBA 05/11/2001 - "We show that quantitative measurements of steady-state levels of subunits by monoclonal antibody reactivity, when used in combination with a discontinuous sucrose gradient methods, provide an improved diagnosis of COX deficiencies by distinguishing between kinetic, stability, and assembly defects. "
9.	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."
10.	BezafibrateIBA 04/19/2012 - "Bezafibrate (BZF), an approved hypolipidemic agent, ameliorates the COX deficiency in mice with mutations in COX10, another COX-assembly gene. " 04/19/2012 - "Copper and bezafibrate cooperate to rescue cytochrome c oxidase deficiency in cells of patients with SCO2 mutations."

Therapies and Procedures

1.	Therapeutics 11/30/2007 - "The zebrafish model has revealed tissue-specific responses to COX deficiency and holds promise for discovery of new therapies to treat mitochondrial diseases in humans." 08/01/1996 - "In this study, we measured responses to combined aerobic training and oral dichloroacetate (DCA) therapy in a 25-year-old woman with a mitochondrial myopathy caused by cytochrome oxidase deficiency. " 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. " 01/01/2018 - "Cytochrome c oxidase deficiency, oxidative stress, possible antioxidant therapy and link to nuclear DNA damage." 03/01/1989 - "Long-term coenzyme Q10 therapy for a mitochondrial encephalomyopathy with cytochrome c oxidase deficiency: a 31P NMR study."
2.	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. "
3.	Surgical Instruments (Clip) 01/01/2015 - "Two-kidney-one-clip (2K1C) hypertension was induced in wild-type (WT) mice and/or those with COX-1 deficiency (COX-1-/-). "
4.	Mechanical Ventilators (Ventilator) 12/01/2001 - "In the affected child maintained on a respirator, simple manipulation of the inspired CO2 tension to establish a normal pressure of 35-45 mmHg automatically caused an increase of serum HCO3- concentration to a normal value of 26.3+/-2.9 mmol/L (and BE to +2.2+/-3.1 mmol/L), in spite of cytochrome oxidase (COX) deficiency due to a confirmed SURF1 mutation. "
5.	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. "