Display Settings:

Format

Send to:

Choose Destination

Cytochrome-c oxidase deficiency

MedGen UID:
75662
Concept ID:
C0268237
Disease or Syndrome
Synonyms: Complex 4 mitochondrial respiratory chain deficiency; Complex IV deficiency; COX deficiency; Cytochrome c oxidase deficiency; Deficiency of mitochondrial respiratory chain complex4; Leigh syndrome, due to COX deficiency; Mitochondrial complex IV deficiency; Mitochondrial Respiratory Chain Complex IV Deficiency; Mitochondrial Respiratory Chain Complex IV Deficiency (mitochondrial genes); Mitochondrial Respiratory Chain Complex IV Deficiency (nuclear genes)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Autosomal recessive inheritance refers to genetic conditions that occur only when mutations are present in both copies of a given gene (i.e., the person is homozygous for a mutation, or carries two different mutations of the same gene, a state referred to as compound heterozygosity).
Mitochondrial inheritance
MedGen UID:
504838
Concept ID:
CN001305
Finding
A mode of inheritance that is observed for traits related to a gene encoded on the mitochondrial genome. Because the mitochondrial genome is essentially always maternally inherited, a mitochondrial condition can only be transmitted by females, although the condition can affect both sexes. The proportion of mutant mitochondria can vary (heteroplasmy).
SNOMED CT: Cytochrome-c oxidase deficiency (67434000); Cytochrome c oxidase deficiency (67434000); COX - Cytochrome C oxidase deficiency (67434000); Complex IV deficiency (67434000)
 
Genes: PET100; COA5; COX20; COX14; APOPT1; TACO1; FASTKD2; COX10; COX6B1
Cytogenetic locations: 12q13.12; 14q32.33; 17p12; 17q23.3; 19p13.2; 19q13.12; 1q44; 2q11.2; 2q33.3
OMIM®: 220110
Orphanet: ORPHA254905

Definition

Complex IV (cytochrome c oxidase; EC 1.9.3.1) 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]

Additional description

From GHR
Cytochrome c oxidase deficiency is a genetic condition that can affect several parts of the body, including the muscles used for movement (skeletal muscles), the heart, the brain, or the liver. Signs and symptoms of cytochrome c oxidase deficiency usually begin before age 2 but can appear later in mildly affected individuals. The severity of cytochrome c oxidase deficiency varies widely among affected individuals, even among those in the same family. People who are mildly affected tend to have muscle weakness (myopathy) and poor muscle tone (hypotonia) with no other health problems. More severely affected people have myopathy along with severe brain dysfunction (encephalomyopathy). Approximately one quarter of individuals with cytochrome c oxidase deficiency have a type of heart disease that enlarges and weakens the heart muscle (hypertrophic cardiomyopathy). Another possible feature of this condition is an enlarged liver, which may lead to liver failure. Most individuals with cytochrome c oxidase deficiency have a buildup of a chemical called lactic acid in the body (lactic acidosis), which can cause nausea and an irregular heart rate, and can be life-threatening. Many people with cytochrome c oxidase deficiency have a specific group of features known as Leigh syndrome. The signs and symptoms of Leigh syndrome include loss of mental function, movement problems, hypertrophic cardiomyopathy, eating difficulties, and brain abnormalities. Cytochrome c oxidase deficiency is one of the many causes of Leigh syndrome. Cytochrome c oxidase deficiency is frequently fatal in childhood, although some individuals with mild signs and symptoms survive into adolescence or adulthood.  http://ghr.nlm.nih.gov/condition/cytochrome-c-oxidase-deficiency

Clinical features

Failure to thrive
MedGen UID:
115900
Concept ID:
C0231246
Sign or Symptom
Slower than normal rate of weight increase.
Glycosuria
MedGen UID:
42267
Concept ID:
C0017979
Finding
The appearance of an abnormally large amount of GLUCOSE in the urine, such as more than 500 mg/day in adults. It can be due to HYPERGLYCEMIA or genetic defects in renal reabsorption (RENAL GLYCOSURIA).
Proteinuria
MedGen UID:
10976
Concept ID:
C0033687
Finding
abnormal presence of protein in urine
Renal Fanconi syndrome
MedGen UID:
341766
Concept ID:
C1857397
Finding
Renal tubular dysfunction
MedGen UID:
504351
Concept ID:
CN000120
Finding
Hyperphosphaturia
MedGen UID:
505453
Concept ID:
CN002803
Finding
An increased excretion of phosphates in the urine.
Aminoaciduria
MedGen UID:
425142
Concept ID:
CN003029
Finding
An increased concentration of an amino acid in the urine.
Ptosis
MedGen UID:
504471
Concept ID:
CN000475
Finding
The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).
Pigmentary retinopathy
MedGen UID:
504507
Concept ID:
CN000544
Finding
Optic atrophy
MedGen UID:
504537
Concept ID:
CN000609
Finding
Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy.
Sensorineural hearing impairment
MedGen UID:
504436
Concept ID:
CN000380
Finding
A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.
Increased CSF lactate
MedGen UID:
257904
Concept ID:
C1167918
Finding
Intellectual disability
MedGen UID:
334384
Concept ID:
C1843367
Finding
Seizures
MedGen UID:
409523
Concept ID:
C1959629
Finding
Ataxia
MedGen UID:
504767
Concept ID:
CN001146
Finding
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- oder overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Global developmental delay
MedGen UID:
504774
Concept ID:
CN001157
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Motor delay
MedGen UID:
504779
Concept ID:
CN001164
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Decreased liver function
MedGen UID:
504835
Concept ID:
CN001291
Finding
Reduced ability of the liver to perform its functions.
Hepatomegaly
MedGen UID:
505165
Concept ID:
CN002031
Finding
Abnormally increased size of the liver.
Increased hepatocellular lipid droplets
MedGen UID:
446768
Concept ID:
CN005720
Finding
An abnormal increase in the amount of intracellular lipid droplets in hepatocytes.
Hypertrophic cardiomyopathy
MedGen UID:
504884
Concept ID:
CN001492
Finding
Hypertrophic cardiomyopathy (HCM) is defined by the presence of increased ventricular wall thickness or mass in the absence of loading conditions (hypertension, valve disease) sufficient to cause the observed abnormality.
Anemia
MedGen UID:
56401
Concept ID:
C0162119
Finding
A laboratory test result which indicates decreased levels of hemoglobin in a biological specimen.
Glycosuria
MedGen UID:
42267
Concept ID:
C0017979
Finding
The appearance of an abnormally large amount of GLUCOSE in the urine, such as more than 500 mg/day in adults. It can be due to HYPERGLYCEMIA or genetic defects in renal reabsorption (RENAL GLYCOSURIA).
Proteinuria
MedGen UID:
10976
Concept ID:
C0033687
Finding
abnormal presence of protein in urine
Increased serum lactate
MedGen UID:
332209
Concept ID:
C1836440
Finding
Lactic acidosis
MedGen UID:
344523
Concept ID:
C1855560
Finding
Hyperphosphaturia
MedGen UID:
505453
Concept ID:
CN002803
Finding
An increased excretion of phosphates in the urine.
Aminoaciduria
MedGen UID:
425142
Concept ID:
CN003029
Finding
An increased concentration of an amino acid in the urine.
Respiratory insufficiency due to muscle weakness
MedGen UID:
332136
Concept ID:
C1836141
Finding
Exertional dyspnea
MedGen UID:
505383
Concept ID:
CN002600
Finding
Respiratory difficulties
MedGen UID:
505386
Concept ID:
CN002605
Finding
Respiratory insufficiency due to muscle weakness
MedGen UID:
332136
Concept ID:
C1836141
Finding
Muscular hypotonia
MedGen UID:
504768
Concept ID:
CN001147
Finding
Muscular hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle), often involving reduced muscle strength. Hypotonia is characterized by a diminished resistance to passive stretching.
Exercise intolerance
MedGen UID:
505555
Concept ID:
CN003200
Finding
Decreased activity of cytochrome C oxidase in muscle tissue
MedGen UID:
505573
Concept ID:
CN003334
Finding
An abnormally reduced activity of the enzyme cytochrome C oxidase in muscle tissue.
Increased intramyocellular lipid droplets
MedGen UID:
489838
Concept ID:
CN168648
Finding
An abnormal increase in intracellular lipid droplets In a muscle. The number and size of these drops can increase with somd disorders of lipid metabolism affecting muscle. See pmid 20691590 for histological images.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews

Recent clinical studies

Etiology

Lopes Costa A, Le Bachelier C, Mathieu L, Rotig A, Boneh A, De Lonlay P, Tarnopolsky MA, Thorburn DR, Bastin J, Djouadi F
Hum Mol Genet 2014 Apr 15;23(8):2106-19. Epub 2013 Dec 23 doi: 10.1093/hmg/ddt603. [Epub ahead of print] PMID: 24365713
Debray FG, Morin C, Janvier A, Villeneuve J, Maranda B, Laframboise R, Lacroix J, Decarie JC, Robitaille Y, Lambert M, Robinson BH, Mitchell GA
J Med Genet 2011 Mar;48(3):183-9. Epub 2011 Jan 25 doi: 10.1136/jmg.2010.081976. [Epub ahead of print] PMID: 21266382
Tellis CM, Rosen C, Close JM, Horton M, Yaruss JS, Verdolini-Abbott K, Sciote JJ
J Voice 2011 Jul;25(4):387-94. Epub 2010 Aug 4 doi: 10.1016/j.jvoice.2010.03.002. [Epub ahead of print] PMID: 20685075Free PMC Article
Diaz F
Biochim Biophys Acta 2010 Jan;1802(1):100-10. Epub 2009 Aug 11 doi: 10.1016/j.bbadis.2009.07.013. [Epub ahead of print] PMID: 19682572
Pickrell AM, Fukui H, Moraes CT
J Bioenerg Biomembr 2009 Oct;41(5):453-6. doi: 10.1007/s10863-009-9245-3. PMID: 19795195

Diagnosis

Kemppainen KK, Rinne J, Sriram A, Lakanmaa M, Zeb A, Tuomela T, Popplestone A, Singh S, Sanz A, Rustin P, Jacobs HT
Hum Mol Genet 2014 Apr 15;23(8):2078-93. Epub 2013 Nov 29 doi: 10.1093/hmg/ddt601. [Epub ahead of print] PMID: 24293544Free PMC Article
Vondrackova A, Vesela K, Hansikova H, Docekalova DZ, Rozsypalova E, Zeman J, Tesarova M
J Hum Genet 2012 Jul;57(7):442-8. Epub 2012 May 17 doi: 10.1038/jhg.2012.49. [Epub ahead of print] PMID: 22592081
Uusimaa J, Jungbluth H, Fratter C, Crisponi G, Feng L, Zeviani M, Hughes I, Treacy EP, Birks J, Brown GK, Sewry CA, McDermott M, Muntoni F, Poulton J
J Med Genet 2011 Oct;48(10):660-8. doi: 10.1136/jmg.2011.089995. PMID: 21931168
Baskin E, Selda Bayrakci U, Alehan F, Ozdemir H, Oner A, Horvath R, Vega-Warner V, Hildebrandt F, Ozaltin F
Pediatr Nephrol 2011 Jul;26(7):1157-61. Epub 2011 Mar 2 doi: 10.1007/s00467-011-1814-0. [Epub ahead of print] PMID: 21365190Free PMC Article
Horvath R, Kemp JP, Tuppen HA, Hudson G, Oldfors A, Marie SK, Moslemi AR, Servidei S, Holme E, Shanske S, Kollberg G, Jayakar P, Pyle A, Marks HM, Holinski-Feder E, Scavina M, Walter MC, Coku J, Günther-Scholz A, Smith PM, McFarland R, Chrzanowska-Lightowlers ZM, Lightowlers RN, Hirano M, Lochmüller H, Taylor RW, Chinnery PF, Tulinius M, DiMauro S
Brain 2009 Nov;132(Pt 11):3165-74. Epub 2009 Aug 31 doi: 10.1093/brain/awp221. [Epub ahead of print] PMID: 19720722Free PMC Article

Therapy

Komaki H, Nishigaki Y, Fuku N, Hosoya H, Murayama K, Ohtake A, Goto Y, Wakamoto H, Koga Y, Tanaka M
Biochim Biophys Acta 2010 Mar;1800(3):313-5. Epub 2009 Jul 17 doi: 10.1016/j.bbagen.2009.07.008. [Epub ahead of print] PMID: 19616603
Böhm M, Pronicka E, Karczmarewicz E, Pronicki M, Piekutowska-Abramczuk D, Sykut-Cegielska J, Mierzewska H, Hansikova H, Vesela K, Tesarova M, Houstkova H, Houstek J, Zeman J
Pediatr Res 2006 Jan;59(1):21-6. Epub 2005 Dec 2 doi: 10.1203/01.pdr.0000190572.68191.13. [Epub ahead of print] PMID: 16326995
Karadag A, Avci Z, Catal F, Odemis E
Fetal Pediatr Pathol 2005 May-Jun;24(3):149-53. doi: 10.1080/15227950500304218. PMID: 16338876
Chariot P, Le Maguet F, Authier FJ, Labes D, Poron F, Gherardi R
Neuropathol Appl Neurobiol 1995 Dec;21(6):540-7. PMID: 8745244
Nozaki H, Hamano S, Ueoka Y, Horita H, Koga Y, Nonaka I
Pediatr Neurol 1990 Sep-Oct;6(5):330-2. PMID: 2173614

Prognosis

Melchionda L, Haack TB, Hardy S, Abbink TE, Fernandez-Vizarra E, Lamantea E, Marchet S, Morandi L, Moggio M, Carrozzo R, Torraco A, Diodato D, Strom TM, Meitinger T, Tekturk P, Yapici Z, Al-Murshedi F, Stevens R, Rodenburg RJ, Lamperti C, Ardissone A, Moroni I, Uziel G, Prokisch H, Taylor RW, Bertini E, van der Knaap MS, Ghezzi D, Zeviani M
Am J Hum Genet 2014 Sep 4;95(3):315-25. Epub 2014 Aug 28 doi: 10.1016/j.ajhg.2014.08.003. [Epub ahead of print] PMID: 25175347Free PMC Article
Lim SC, Smith KR, Stroud DA, Compton AG, Tucker EJ, Dasvarma A, Gandolfo LC, Marum JE, McKenzie M, Peters HL, Mowat D, Procopis PG, Wilcken B, Christodoulou J, Brown GK, Ryan MT, Bahlo M, Thorburn DR
Am J Hum Genet 2014 Feb 6;94(2):209-22. Epub 2014 Jan 23 doi: 10.1016/j.ajhg.2013.12.015. [Epub ahead of print] PMID: 24462369Free PMC Article
Vondrackova A, Vesela K, Hansikova H, Docekalova DZ, Rozsypalova E, Zeman J, Tesarova M
J Hum Genet 2012 Jul;57(7):442-8. Epub 2012 May 17 doi: 10.1038/jhg.2012.49. [Epub ahead of print] PMID: 22592081
Debray FG, Morin C, Janvier A, Villeneuve J, Maranda B, Laframboise R, Lacroix J, Decarie JC, Robitaille Y, Lambert M, Robinson BH, Mitchell GA
J Med Genet 2011 Mar;48(3):183-9. Epub 2011 Jan 25 doi: 10.1136/jmg.2010.081976. [Epub ahead of print] PMID: 21266382
Horvath R, Kemp JP, Tuppen HA, Hudson G, Oldfors A, Marie SK, Moslemi AR, Servidei S, Holme E, Shanske S, Kollberg G, Jayakar P, Pyle A, Marks HM, Holinski-Feder E, Scavina M, Walter MC, Coku J, Günther-Scholz A, Smith PM, McFarland R, Chrzanowska-Lightowlers ZM, Lightowlers RN, Hirano M, Lochmüller H, Taylor RW, Chinnery PF, Tulinius M, DiMauro S
Brain 2009 Nov;132(Pt 11):3165-74. Epub 2009 Aug 31 doi: 10.1093/brain/awp221. [Epub ahead of print] PMID: 19720722Free PMC Article

Clinical prediction guides

Melchionda L, Haack TB, Hardy S, Abbink TE, Fernandez-Vizarra E, Lamantea E, Marchet S, Morandi L, Moggio M, Carrozzo R, Torraco A, Diodato D, Strom TM, Meitinger T, Tekturk P, Yapici Z, Al-Murshedi F, Stevens R, Rodenburg RJ, Lamperti C, Ardissone A, Moroni I, Uziel G, Prokisch H, Taylor RW, Bertini E, van der Knaap MS, Ghezzi D, Zeviani M
Am J Hum Genet 2014 Sep 4;95(3):315-25. Epub 2014 Aug 28 doi: 10.1016/j.ajhg.2014.08.003. [Epub ahead of print] PMID: 25175347Free PMC Article
Lim SC, Smith KR, Stroud DA, Compton AG, Tucker EJ, Dasvarma A, Gandolfo LC, Marum JE, McKenzie M, Peters HL, Mowat D, Procopis PG, Wilcken B, Christodoulou J, Brown GK, Ryan MT, Bahlo M, Thorburn DR
Am J Hum Genet 2014 Feb 6;94(2):209-22. Epub 2014 Jan 23 doi: 10.1016/j.ajhg.2013.12.015. [Epub ahead of print] PMID: 24462369Free PMC Article
Vondrackova A, Vesela K, Hansikova H, Docekalova DZ, Rozsypalova E, Zeman J, Tesarova M
J Hum Genet 2012 Jul;57(7):442-8. Epub 2012 May 17 doi: 10.1038/jhg.2012.49. [Epub ahead of print] PMID: 22592081
Debray FG, Morin C, Janvier A, Villeneuve J, Maranda B, Laframboise R, Lacroix J, Decarie JC, Robitaille Y, Lambert M, Robinson BH, Mitchell GA
J Med Genet 2011 Mar;48(3):183-9. Epub 2011 Jan 25 doi: 10.1136/jmg.2010.081976. [Epub ahead of print] PMID: 21266382
Yu-Wai-Man P, Sitarz KS, Samuels DC, Griffiths PG, Reeve AK, Bindoff LA, Horvath R, Chinnery PF
Hum Mol Genet 2010 Aug 1;19(15):3043-52. Epub 2010 May 18 doi: 10.1093/hmg/ddq209. [Epub ahead of print] PMID: 20484224Free PMC Article

Recent systematic reviews

Hirano M, Angelini C, Montagna P, Hays AP, Tanji K, Mitsumoto H, Gordon PH, Naini AB, DiMauro S, Rowland LP
Arch Neurol 2008 Mar;65(3):403-6. doi: 10.1001/archneurol.2007.65. PMID: 18332255
Tiranti V, Munaro M, Sandonà D, Lamantea E, Rimoldi M, DiDonato S, Bisson R, Zeviani M
Hum Mol Genet 1995 Nov;4(11):2017-23. PMID: 8589677

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...