KEGG   DISEASE: Combined oxidative phosphorylation deficiencyHelp
Entry
H00891                      Disease                                

Name
Combined oxidative phosphorylation deficiency
  Supergrp
Mitochondrial disease [DS:H01427]
Description
Combined oxidative phosphorylation deficiency (COXPD) is a group of multisystem disorders with variable manifestations resulting from a defect in the mitochondrial oxidative phosphorylation system. It has been reported that the mutations in the ribosomal protein gene (MRPS16 and MRPS22) cause severe antenatal-onset infantile disease. The patients with COXPD caused by mutations in mitochondrial translation elongation factor genes (GFM1, TUFM, TSFM and C12orf65) have also been reported.
Category
Inherited metabolic disease; Mitochondrial disease
Brite
Human diseases [BR:br08402]
 Congenital disorders of metabolism
  Mitochondrial diseases
   H00891  Combined oxidative phosphorylation deficiency
Human diseases in ICD-11 classification [BR:br08403]
 05 Endocrine, nutritional or metabolic diseases
  Metabolic disorders
   Inborn errors of metabolism
    5C53  Inborn errors of energy metabolism
     H00891  Combined oxidative phosphorylation deficiency
BRITE hierarchy
Gene
(COXPD1) GFM1 [HSA:85476] [KO:K02355]
(COXPD2) MRPS16 [HSA:51021] [KO:K02959]
(COXPD3) TSFM [HSA:10102] [KO:K02357]
(COXPD4) TUFM [HSA:7284] [KO:K02358]
(COXPD5) MRPS22 [HSA:56945] [KO:K17401]
(COXPD6) AIFM1 [HSA:9131] [KO:K04727]
(COXPD7) C12orf65 [HSA:91574] [KO:K23498]
(COXPD8) AARS2 [HSA:57505] [KO:K01872]
(COXPD9) MRPL3 [HSA:11222] [KO:K02906]
(COXPD10) MTO1 [HSA:25821] [KO:K03495]
(COXPD11) RMND1 [HSA:55005] [KO:K23499]
(COXPD12) EARS2 [HSA:124454] [KO:K01885]
(COXPD13) PNPT1 [HSA:87178] [KO:K00962]
(COXPD14) FARS2 [HSA:10667] [KO:K01889]
(COXPD15) MTFMT [HSA:123263] [KO:K00604]
(COXPD16) MRPL44 [HSA:65080] [KO:K17425]
(COXPD17) ELAC2 [HSA:60528] [KO:K00784]
(COXPD18) SFXN4 [HSA:119559] [KO:K23502]
(COXPD19) LYRM4 [HSA:57128] [KO:K22069]
(COXPD20) VARS2 [HSA:57176] [KO:K01873]
(COXPD21) TARS2 [HSA:80222] [KO:K01868]
(COXPD22) ATP5A1 [HSA:498] [KO:K02132]
(COXPD23) GTPBP3 [HSA:84705] [KO:K03650]
(COXPD24) NARS2 [HSA:79731] [KO:K01893]
(COXPD25) MARS2 [HSA:92935] [KO:K01874]
(COXPD26) TRMT5 [HSA:57570] [KO:K15429]
(COXPD27) CARS2 [HSA:79587] [KO:K01883]
(COXPD28) SLC25A26 [HSA:115286] [KO:K15111]
(COXPD29) TXN2 [HSA:25828] [KO:K03671]
(COXPD30) TRMT10C [HSA:54931] [KO:K17654]
(COXPD31) MIPEP [HSA:4285] [KO:K01410]
(COXPD32) MRPS34 [HSA:65993] [KO:K17412]
(COXPD33) C1QBP [HSA:708] [KO:K15414]
Other DBs
ICD-11: 5C53.2Y
ICD-10: E88.8
MeSH: C563797 C566468 C566467 C565690 C567126
OMIM: 609060 610498 610505 610678 611719 300816 613559 614096 614582 614702 614922 614924 614932 614946 614947 615395 615440 615578 615595 615917 615918 616045 616198 616239 616430 616539 616672 616794 616811 616974 617228 617664 617713
Reference
  Authors
Kemp JP, Smith PM, Pyle A, Neeve VC, Tuppen HA, Schara U, Talim B, Topaloglu H, Holinski-Feder E, Abicht A, Czermin B, Lochmuller H, McFarland R, Chinnery PF, Chrzanowska-Lightowlers ZM, Lightowlers RN, Taylor RW, Horvath R
  Title
Nuclear factors involved in mitochondrial translation cause a subgroup of combined respiratory chain deficiency.
  Journal
Brain 134:183-95 (2011)
DOI:10.1093/brain/awq320
Reference
  Authors
Miller C, Saada A, Shaul N, Shabtai N, Ben-Shalom E, Shaag A, Hershkovitz E, Elpeleg O
  Title
Defective mitochondrial translation caused by a ribosomal protein (MRPS16) mutation.
  Journal
Ann Neurol 56:734-8 (2004)
DOI:10.1002/ana.20282
Reference
  Authors
Smeitink JA, Elpeleg O, Antonicka H, Diepstra H, Saada A, Smits P, Sasarman F, Vriend G, Jacob-Hirsch J, Shaag A, Rechavi G, Welling B, Horst J, Rodenburg RJ, van den Heuvel B, Shoubridge EA
  Title
Distinct clinical phenotypes associated with a mutation in the mitochondrial translation elongation factor EFTs.
  Journal
Am J Hum Genet 79:869-77 (2006)
DOI:10.1086/508434
Reference
  Authors
Valente L, Tiranti V, Marsano RM, Malfatti E, Fernandez-Vizarra E, Donnini C, Mereghetti P, De Gioia L, Burlina A, Castellan C, Comi GP, Savasta S, Ferrero I, Zeviani M
  Title
Infantile encephalopathy and defective mitochondrial DNA translation in patients with mutations of mitochondrial elongation factors EFG1 and EFTu.
  Journal
Am J Hum Genet 80:44-58 (2007)
DOI:10.1086/510559
Reference
  Authors
Saada A, Shaag A, Arnon S, Dolfin T, Miller C, Fuchs-Telem D, Lombes A, Elpeleg O
  Title
Antenatal mitochondrial disease caused by mitochondrial ribosomal protein (MRPS22) mutation.
  Journal
J Med Genet 44:784-6 (2007)
DOI:10.1136/jmg.2007.053116
Reference
  Authors
Ghezzi D, Sevrioukova I, Invernizzi F, Lamperti C, Mora M, D'Adamo P, Novara F, Zuffardi O, Uziel G, Zeviani M
  Title
Severe X-linked mitochondrial encephalomyopathy associated with a mutation in apoptosis-inducing factor.
  Journal
Am J Hum Genet 86:639-49 (2010)
DOI:10.1016/j.ajhg.2010.03.002
Reference
  Authors
Antonicka H, Ostergaard E, Sasarman F, Weraarpachai W, Wibrand F, Pedersen AM, Rodenburg RJ, van der Knaap MS, Smeitink JA, Chrzanowska-Lightowlers ZM, Shoubridge EA
  Title
Mutations in C12orf65 in patients with encephalomyopathy and a mitochondrial translation defect.
  Journal
Am J Hum Genet 87:115-22 (2010)
DOI:10.1016/j.ajhg.2010.06.004
Reference
  Authors
Steenweg ME, Ghezzi D, Haack T, Abbink TE, Martinelli D, van Berkel CG, Bley A, Diogo L, Grillo E, Te Water Naude J, Strom TM, Bertini E, Prokisch H, van der Knaap MS, Zeviani M
  Title
Leukoencephalopathy with thalamus and brainstem involvement and high lactate 'LTBL' caused by EARS2 mutations.
  Journal
Brain 135:1387-94 (2012)
DOI:10.1093/brain/aws070
Reference
  Authors
Vedrenne V, Gowher A, De Lonlay P, Nitschke P, Serre V, Boddaert N, Altuzarra C, Mager-Heckel AM, Chretien F, Entelis N, Munnich A, Tarassov I, Rotig A
  Title
Mutation in PNPT1, which encodes a polyribonucleotide nucleotidyltransferase, impairs RNA import into mitochondria and causes respiratory-chain deficiency.
  Journal
Am J Hum Genet 91:912-8 (2012)
DOI:10.1016/j.ajhg.2012.09.001
Reference
  Authors
Almalki A, Alston CL, Parker A, Simonic I, Mehta SG, He L, Reza M, Oliveira JM, Lightowlers RN, McFarland R, Taylor RW, Chrzanowska-Lightowlers ZM
  Title
Mutation of the human mitochondrial phenylalanine-tRNA synthetase causes infantile-onset epilepsy and cytochrome c oxidase deficiency.
  Journal
Biochim Biophys Acta 1842:56-64 (2014)
DOI:10.1016/j.bbadis.2013.10.008
Reference
  Authors
Neeve VC, Pyle A, Boczonadi V, Gomez-Duran A, Griffin H, Santibanez-Koref M, Gaiser U, Bauer P, Tzschach A, Chinnery PF, Horvath R
  Title
Clinical and functional characterisation of the combined respiratory chain defect in two sisters due to autosomal recessive mutations in MTFMT.
  Journal
Mitochondrion 13:743-8 (2013)
DOI:10.1016/j.mito.2013.03.002
Reference
  Authors
Taylor RW, Pyle A, Griffin H, Blakely EL, Duff J, He L, Smertenko T, Alston CL, Neeve VC, Best A, Yarham JW, Kirschner J, Schara U, Talim B, Topaloglu H, Baric I, Holinski-Feder E, Abicht A, Czermin B, Kleinle S, Morris AA, Vassallo G, Gorman GS, Ramesh V, Turnbull DM, Santibanez-Koref M, McFarland R, Horvath R, Chinnery PF
  Title
Use of whole-exome sequencing to determine the genetic basis of multiple mitochondrial respiratory chain complex deficiencies.
  Journal
JAMA 312:68-77 (2014)
DOI:10.1001/jama.2014.7184
Reference
  Authors
Carroll CJ, Isohanni P, Poyhonen R, Euro L, Richter U, Brilhante V, Gotz A, Lahtinen T, Paetau A, Pihko H, Battersby BJ, Tyynismaa H, Suomalainen A
  Title
Whole-exome sequencing identifies a mutation in the mitochondrial ribosome protein MRPL44 to underlie mitochondrial infantile cardiomyopathy.
  Journal
J Med Genet 50:151-9 (2013)
DOI:10.1136/jmedgenet-2012-101375
Reference
  Authors
Haack TB, Kopajtich R, Freisinger P, Wieland T, Rorbach J, Nicholls TJ, Baruffini E, Walther A, Danhauser K, Zimmermann FA, Husain RA, Schum J, Mundy H, Ferrero I, Strom TM, Meitinger T, Taylor RW, Minczuk M, Mayr JA, Prokisch H
  Title
ELAC2 mutations cause a mitochondrial RNA processing defect associated with hypertrophic cardiomyopathy.
  Journal
Am J Hum Genet 93:211-23 (2013)
DOI:10.1016/j.ajhg.2013.06.006
Reference
  Authors
Hildick-Smith GJ, Cooney JD, Garone C, Kremer LS, Haack TB, Thon JN, Miyata N, Lieber DS, Calvo SE, Akman HO, Yien YY, Huston NC, Branco DS, Shah DI, Freedman ML, Koehler CM, Italiano JE Jr, Merkenschlager A, Beblo S, Strom TM, Meitinger T, Freisinger P, Donati MA, Prokisch H, Mootha VK, DiMauro S, Paw BH
  Title
Macrocytic anemia and mitochondriopathy resulting from a defect in sideroflexin 4.
  Journal
Am J Hum Genet 93:906-14 (2013)
DOI:10.1016/j.ajhg.2013.09.011
Reference
  Authors
Galmiche L, Serre V, Beinat M, Assouline Z, Lebre AS, Chretien D, Nietschke P, Benes V, Boddaert N, Sidi D, Brunelle F, Rio M, Munnich A, Rotig A
  Title
Exome sequencing identifies MRPL3 mutation in mitochondrial cardiomyopathy.
  Journal
Hum Mutat 32:1225-31 (2011)
DOI:10.1002/humu.21562
Reference
  Authors
Lim SC, Friemel M, Marum JE, Tucker EJ, Bruno DL, Riley LG, Christodoulou J, Kirk EP, Boneh A, DeGennaro CM, Springer M, Mootha VK, Rouault TA, Leimkuhler S, Thorburn DR, Compton AG
  Title
Mutations in LYRM4, encoding iron-sulfur cluster biogenesis factor ISD11, cause deficiency of multiple respiratory chain complexes.
  Journal
Hum Mol Genet 22:4460-73 (2013)
DOI:10.1093/hmg/ddt295
Reference
  Authors
Diodato D, Melchionda L, Haack TB, Dallabona C, Baruffini E, Donnini C, Granata T, Ragona F, Balestri P, Margollicci M, Lamantea E, Nasca A, Powell CA, Minczuk M, Strom TM, Meitinger T, Prokisch H, Lamperti C, Zeviani M, Ghezzi D
  Title
VARS2 and TARS2 mutations in patients with mitochondrial encephalomyopathies.
  Journal
Hum Mutat 35:983-9 (2014)
DOI:10.1002/humu.22590
Reference
  Authors
Lieber DS, Calvo SE, Shanahan K, Slate NG, Liu S, Hershman SG, Gold NB, Chapman BA, Thorburn DR, Berry GT, Schmahmann JD, Borowsky ML, Mueller DM, Sims KB, Mootha VK
  Title
Targeted exome sequencing of suspected mitochondrial disorders.
  Journal
Neurology 80:1762-70 (2013)
DOI:10.1212/WNL.0b013e3182918c40
Reference
  Authors
Kopajtich R, Nicholls TJ, Rorbach J, Metodiev MD, Freisinger P, Mandel H, Vanlander A, Ghezzi D, Carrozzo R, Taylor RW, Marquard K, Murayama K, Wieland T, Schwarzmayr T, Mayr JA, Pearce SF, Powell CA, Saada A, Ohtake A, Invernizzi F, Lamantea E, Sommerville EW, Pyle A, Chinnery PF, Crushell E, Okazaki Y, Kohda M, Kishita Y, Tokuzawa Y, Assouline Z, Rio M, Feillet F, Mousson de Camaret B, Chretien D, Munnich A, Menten B, Sante T, Smet J, Regal L, Lorber A, Khoury A, Zeviani M, Strom TM, Meitinger T, Bertini ES, Van Coster R, Klopstock T, Rotig A, Haack TB, Minczuk M, Prokisch H
  Title
Mutations in GTPBP3 cause a mitochondrial translation defect associated with hypertrophic cardiomyopathy, lactic acidosis, and encephalopathy.
  Journal
Am J Hum Genet 95:708-20 (2014)
DOI:10.1016/j.ajhg.2014.10.017
Reference
  Authors
Sofou K, Kollberg G, Holmstrom M, Davila M, Darin N, Gustafsson CM, Holme E, Oldfors A, Tulinius M, Asin-Cayuela J
  Title
Whole exome sequencing reveals mutations in NARS2 and PARS2, encoding the mitochondrial asparaginyl-tRNA synthetase and prolyl-tRNA synthetase, in patients with Alpers syndrome.
  Journal
Mol Genet Genomic Med 3:59-68 (2015)
DOI:10.1002/mgg3.115
Reference
  Authors
Webb BD, Wheeler PG, Hagen JJ, Cohen N, Linderman MD, Diaz GA, Naidich TP, Rodenburg RJ, Houten SM, Schadt EE
  Title
Novel, compound heterozygous, single-nucleotide variants in MARS2 associated with developmental delay, poor growth, and sensorineural hearing loss.
  Journal
Hum Mutat 36:587-92 (2015)
DOI:10.1002/humu.22781
Reference
  Authors
Powell CA, Kopajtich R, D'Souza AR, Rorbach J, Kremer LS, Husain RA, Dallabona C, Donnini C, Alston CL, Griffin H, Pyle A, Chinnery PF, Strom TM, Meitinger T, Rodenburg RJ, Schottmann G, Schuelke M, Romain N, Haller RG, Ferrero I, Haack TB, Taylor RW, Prokisch H, Minczuk M
  Title
TRMT5 Mutations Cause a Defect in Post-transcriptional Modification of Mitochondrial tRNA Associated with Multiple Respiratory-Chain Deficiencies.
  Journal
Am J Hum Genet 97:319-28 (2015)
DOI:10.1016/j.ajhg.2015.06.011
Reference
  Authors
Coughlin CR 2nd, Scharer GH, Friederich MW, Yu HC, Geiger EA, Creadon-Swindell G, Collins AE, Vanlander AV, Coster RV, Powell CA, Swanson MA, Minczuk M, Van Hove JL, Shaikh TH
  Title
Mutations in the mitochondrial cysteinyl-tRNA synthase gene, CARS2, lead to a severe epileptic encephalopathy and complex movement disorder.
  Journal
J Med Genet 52:532-40 (2015)
DOI:10.1136/jmedgenet-2015-103049
Reference
  Authors
Kishita Y, Pajak A, Bolar NA, Marobbio CM, Maffezzini C, Miniero DV, Monne M, Kohda M, Stranneheim H, Murayama K, Naess K, Lesko N, Bruhn H, Mourier A, Wibom R, Nennesmo I, Jespers A, Govaert P, Ohtake A, Van Laer L, Loeys BL, Freyer C, Palmieri F, Wredenberg A, Okazaki Y, Wedell A
  Title
Intra-mitochondrial Methylation Deficiency Due to Mutations in SLC25A26.
  Journal
Am J Hum Genet 97:761-8 (2015)
DOI:10.1016/j.ajhg.2015.09.013
Reference
  Authors
Holzerova E, Danhauser K, Haack TB, Kremer LS, Melcher M, Ingold I, Kobayashi S, Terrile C, Wolf P, Schaper J, Mayatepek E, Baertling F, Friedmann Angeli JP, Conrad M, Strom TM, Meitinger T, Prokisch H, Distelmaier F
  Title
Human thioredoxin 2 deficiency impairs mitochondrial redox homeostasis and causes early-onset neurodegeneration.
  Journal
Brain 139:346-54 (2016)
DOI:10.1093/brain/awv350
Reference
  Authors
Metodiev MD, Thompson K, Alston CL, Morris AA, He L, Assouline Z, Rio M, Bahi-Buisson N, Pyle A, Griffin H, Siira S, Filipovska A, Munnich A, Chinnery PF, McFarland R, Rotig A, Taylor RW
  Title
Recessive Mutations in TRMT10C Cause Defects in Mitochondrial RNA Processing and Multiple Respiratory Chain Deficiencies.
  Journal
Am J Hum Genet 98:993-1000 (2016)
DOI:10.1016/j.ajhg.2016.03.010
Reference
  Authors
Eldomery MK, Akdemir ZC, Vogtle FN, Charng WL, Mulica P, Rosenfeld JA, Gambin T, Gu S, Burrage LC, Al Shamsi A, Penney S, Jhangiani SN, Zimmerman HH, Muzny DM, Wang X, Tang J, Medikonda R, Ramachandran PV, Wong LJ, Boerwinkle E, Gibbs RA, Eng CM, Lalani SR, Hertecant J, Rodenburg RJ, Abdul-Rahman OA, Yang Y, Xia F, Wang MC, Lupski JR, Meisinger C, Sutton VR
  Title
MIPEP recessive variants cause a syndrome of left ventricular non-compaction, hypotonia, and infantile death.
  Journal
Genome Med 8:106 (2016)
DOI:10.1186/s13073-016-0360-6
Reference
  Authors
Lake NJ, Webb BD, Stroud DA, Richman TR, Ruzzenente B, Compton AG, Mountford HS, Pulman J, Zangarelli C, Rio M, Boddaert N, Assouline Z, Sherpa MD, Schadt EE, Houten SM, Byrnes J, McCormick EM, Zolkipli-Cunningham Z, Haude K, Zhang Z, Retterer K, Bai R, Calvo SE, Mootha VK, Christodoulou J, Rotig A, Filipovska A, Cristian I, Falk MJ, Metodiev MD, Thorburn DR
  Title
Biallelic Mutations in MRPS34 Lead to Instability of the Small Mitoribosomal Subunit and Leigh Syndrome.
  Journal
Am J Hum Genet 101:239-254 (2017)
DOI:10.1016/j.ajhg.2017.07.005
Reference
  Authors
Feichtinger RG, Olahova M, Kishita Y, Garone C, Kremer LS, Yagi M, Uchiumi T, Jourdain AA, Thompson K, D'Souza AR, Kopajtich R, Alston CL, Koch J, Sperl W, Mastantuono E, Strom TM, Wortmann SB, Meitinger T, Pierre G, Chinnery PF, Chrzanowska-Lightowlers ZM, Lightowlers RN, DiMauro S, Calvo SE, Mootha VK, Moggio M, Sciacco M, Comi GP, Ronchi D, Murayama K, Ohtake A, Rebelo-Guiomar P, Kohda M, Kang D, Mayr JA, Taylor RW, Okazaki Y, Minczuk M, Prokisch H
  Title
Biallelic C1QBP Mutations Cause Severe Neonatal-, Childhood-, or Later-Onset Cardiomyopathy Associated with Combined Respiratory-Chain Deficiencies.
  Journal
Am J Hum Genet 101:525-538 (2017)
DOI:10.1016/j.ajhg.2017.08.015

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