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Cytochrome-c oxidase deficiency

MedGen UID:
75662
•Concept ID:
C0268237
•
Disease or Syndrome
Synonym: Cytochrome-c oxidase deficiency disease
SNOMED CT: Cytochrome-c oxidase deficiency (67434000); Cytochrome c oxidase deficiency (67434000); COX - Cytochrome C oxidase deficiency (67434000); Complex IV deficiency (67434000); Mitochondrial complex IV deficiency (67434000)
 
Monarch Initiative: MONDO:0009068
OMIM®: 220110; 516030; 516040; 516050; 590010; 590050

Definition

A very rare inherited metabolic disorder characterized by deficiency of the enzyme cytochrome-C oxidase. It may be manifested as an isolated myopathy or a systemic disorder. Signs and symptoms include myotonia, dysfunction of the heart, kidney, and brain, and lactic acidosis. [from NCI]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • Cytochrome-c oxidase deficiency
Follow this link to review classifications for Cytochrome-c oxidase deficiency in Orphanet.

Professional guidelines

PubMed

Genotypes and clinical phenotypes in children with cytochrome-c oxidase deficiency.
Darin N, Moslemi AR, Lebon S, Rustin P, Holme E, Oldfors A, Tulinius M
Neuropediatrics 2003 Dec;34(6):311-7. doi: 10.1055/s-2003-44670. PMID: 14681757
Prenatal diagnosis of cytochrome c oxidase deficiency in cultured amniocytes is hazardous.
Bourgeron T, Chrétien D, Rötig A, Munnich A, Rustin P
Prenat Diagn 1992 Jun;12(6):548-9. doi: 10.1002/pd.1970120614. PMID: 1325051
Prenatal diagnosis of cytochrome c oxidase deficiency by biopsy of chorionic villi.
Ruitenbeek W, Sengers R, Albani M, Trijbels F, Janssen A, van Diggelen O, Bakkeren J
N Engl J Med 1988 Oct 20;319(16):1095. doi: 10.1056/NEJM198810203191616. PMID: 2845269

Recent clinical studies

Etiology

Cytochrome c oxidase deficiency: patients and animal models.
Diaz F
Biochim Biophys Acta 2010 Jan;1802(1):100-10. Epub 2009 Aug 11 doi: 10.1016/j.bbadis.2009.07.013. PMID: 19682572
Mitochondrial disorders.
Schapira AH
Curr Opin Neurol 2000 Oct;13(5):527-32. doi: 10.1097/00019052-200010000-00004. PMID: 11073358
Human cytochrome oxidase deficiency.
Robinson BH
Pediatr Res 2000 Nov;48(5):581-5. doi: 10.1203/00006450-200011000-00004. PMID: 11044474
Human cytochrome c oxidase: structure, function, and deficiency.
Taanman JW
J Bioenerg Biomembr 1997 Apr;29(2):151-63. doi: 10.1023/a:1022638013825. PMID: 9239540
Mitochondrial myopathies.
DiMauro S, Bonilla E, Zeviani M, Servidei S, DeVivo DC, Schon EA
J Inherit Metab Dis 1987;10 Suppl 1:113-28. doi: 10.1007/BF01812852. PMID: 2824920

Diagnosis

Cytochrome c oxidase deficiency detection in human fibroblasts using scanning electrochemical microscopy.
Thind S, Lima D, Booy E, Trinh D, McKenna SA, Kuss S
Proc Natl Acad Sci U S A 2024 Jan 2;121(1):e2310288120. Epub 2023 Dec 28 doi: 10.1073/pnas.2310288120. PMID: 38154062Free PMC Article
Mitochondrial cytochrome c oxidase deficiency.
Rak M, Bénit P, Chrétien D, Bouchereau J, Schiff M, El-Khoury R, Tzagoloff A, Rustin P
Clin Sci (Lond) 2016 Mar;130(6):393-407. doi: 10.1042/CS20150707. PMID: 26846578Free PMC Article
Diagnosis and treatment of mitochondrial myopathies.
Pfeffer G, Chinnery PF
Ann Med 2013 Feb;45(1):4-16. Epub 2011 Aug 25 doi: 10.3109/07853890.2011.605389. PMID: 21867371Free PMC Article
Cytochrome c oxidase deficiency.
Shoubridge EA
Am J Med Genet 2001 Spring;106(1):46-52. doi: 10.1002/ajmg.1378. PMID: 11579424
Neuropathologic aspects of cytochrome C oxidase deficiency.
Tanji K, Bonilla E
Brain Pathol 2000 Jul;10(3):422-30. doi: 10.1111/j.1750-3639.2000.tb00274.x. PMID: 10885661Free PMC Article

Therapy

Alterations of sirtuins in mitochondrial cytochrome c-oxidase deficiency.
Potthast AB, Heuer T, Warneke SJ, Das AM
PLoS One 2017;12(10):e0186517. Epub 2017 Oct 23 doi: 10.1371/journal.pone.0186517. PMID: 29059204Free PMC Article
Mutations in COA6 cause cytochrome c oxidase deficiency and neonatal hypertrophic cardiomyopathy.
Baertling F, A M van den Brand M, Hertecant JL, Al-Shamsi A, P van den Heuvel L, Distelmaier F, Mayatepek E, Smeitink JA, Nijtmans LG, Rodenburg RJ
Hum Mutat 2015 Jan;36(1):34-8. Epub 2014 Nov 18 doi: 10.1002/humu.22715. PMID: 25339201
Diagnosis and treatment of mitochondrial myopathies.
Pfeffer G, Chinnery PF
Ann Med 2013 Feb;45(1):4-16. Epub 2011 Aug 25 doi: 10.3109/07853890.2011.605389. PMID: 21867371Free PMC Article
Mitochondrial disorders.
Schapira AH
Curr Opin Neurol 2000 Oct;13(5):527-32. doi: 10.1097/00019052-200010000-00004. PMID: 11073358
Mitochondria and ageing.
Müller-Höcker J
Brain Pathol 1992 Apr;2(2):149-58. doi: 10.1111/j.1750-3639.1992.tb00683.x. PMID: 1341956

Prognosis

Novel p.P298L SURF1 mutation in thiamine deficient Leigh syndrome patients compromises cytochrome c oxidase activity.
Mani S, Chandak GR, Singh KK, Singh R, Rao SN
Mitochondrion 2020 Jul;53:91-98. Epub 2020 May 4 doi: 10.1016/j.mito.2020.04.009. PMID: 32380162
COX6A2 variants cause a muscle-specific cytochrome c oxidase deficiency.
Inoue M, Uchino S, Iida A, Noguchi S, Hayashi S, Takahashi T, Fujii K, Komaki H, Takeshita E, Nonaka I, Okada Y, Yoshizawa T, Van Lommel L, Schuit F, Goto YI, Mimaki M, Nishino I
Ann Neurol 2019 Aug;86(2):193-202. Epub 2019 Jul 2 doi: 10.1002/ana.25517. PMID: 31155743
A novel histochemistry assay to assess and quantify focal cytochrome c oxidase deficiency.
Simard ML, Mourier A, Greaves LC, Taylor RW, Stewart JB
J Pathol 2018 Jul;245(3):311-323. Epub 2018 May 14 doi: 10.1002/path.5084. PMID: 29660116Free PMC Article
Mitochondrial cytochrome c oxidase deficiency.
Rak M, Bénit P, Chrétien D, Bouchereau J, Schiff M, El-Khoury R, Tzagoloff A, Rustin P
Clin Sci (Lond) 2016 Mar;130(6):393-407. doi: 10.1042/CS20150707. PMID: 26846578Free PMC Article
Genetic defects of cytochrome c oxidase assembly.
Pecina P, Houstková H, Hansíková H, Zeman J, Houstek J
Physiol Res 2004;53 Suppl 1:S213-23. PMID: 15119951

Clinical prediction guides

A novel histochemistry assay to assess and quantify focal cytochrome c oxidase deficiency.
Simard ML, Mourier A, Greaves LC, Taylor RW, Stewart JB
J Pathol 2018 Jul;245(3):311-323. Epub 2018 May 14 doi: 10.1002/path.5084. PMID: 29660116Free PMC Article
Alterations of sirtuins in mitochondrial cytochrome c-oxidase deficiency.
Potthast AB, Heuer T, Warneke SJ, Das AM
PLoS One 2017;12(10):e0186517. Epub 2017 Oct 23 doi: 10.1371/journal.pone.0186517. PMID: 29059204Free PMC Article
Mitochondrial cytochrome c oxidase deficiency.
Rak M, Bénit P, Chrétien D, Bouchereau J, Schiff M, El-Khoury R, Tzagoloff A, Rustin P
Clin Sci (Lond) 2016 Mar;130(6):393-407. doi: 10.1042/CS20150707. PMID: 26846578Free PMC Article
Human cytochrome c oxidase: structure, function, and deficiency.
Taanman JW
J Bioenerg Biomembr 1997 Apr;29(2):151-63. doi: 10.1023/a:1022638013825. PMID: 9239540
Mitochondria and ageing.
Müller-Höcker J
Brain Pathol 1992 Apr;2(2):149-58. doi: 10.1111/j.1750-3639.1992.tb00683.x. PMID: 1341956

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