KEGG   DISEASE: Mitochondrial respiratory chain deficiencies (MRCD)Help
Entry
H00473                      Disease                                

Name
Mitochondrial respiratory chain deficiencies (MRCD), including:
Mitochondrial complex I deficiency (MT-C1D);
Complex II deficiency (MT-C2D);
Complex III deficiency (MT-C3D);
Leigh syndrome (LS) [DS:H01354];
Leber Hereditary Optic Neuropathy (LHON) [DS:H00068];
Leber Optic Atrophy and Dystonia (LDYT) [DS:H01365];
MELAS Syndrome [DS:H01347];
Kearns-Sayre Syndrome (KSS) [DS:H01355];
GRACILE Syndrome
Description
Mitochondrial respiratory chain deficiencies (MRCD) are a group of disorders of adults and children, with highly variable phenotypes that include macrocephaly with progressive leukodystrophy, encephalopathy (including MELAS), cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease and Alzheimer's disease.
Category
Inherited metabolic disease; Mitochondrial disease
Brite
Human diseases [BR:br08402]
 Congenital disorders of metabolism
  Mitochondrial diseases
   H00473  Mitochondrial respiratory chain deficiencies (MRCD)
Human diseases in ICD-10 classification [BR:br08403]
 4. Endocrine, nutritional and metabolic diseases (E00-E90)
  E70-E90  Metabolic disorders
   E88  Other metabolic disorders
    H00473  Mitochondrial respiratory chain deficiencies (MRCD)
BRITE hierarchy
Pathway
Oxidative phosphorylation
Gene
(MT-C1D) NDUFS1 [HSA:4719] [KO:K03934]
(MT-C1D) NDUFS2 [HSA:4720] [KO:K03935]
(MT-C1D/LS) NDUFS3 [HSA:4722] [KO:K03936]
(MT-C1D/LS) NDUFS4 [HSA:4724] [KO:K03937]
(MT-C1D) NDUFS6 [HSA:4726] [KO:K03939]
(MT-C1D/LS) NDUFS7 [HSA:374291] [KO:K03940]
(MT-C1D/LS) NDUFS8 [HSA:4728] [KO:K03941]
(MT-C1D) NDUFA1 [HSA:4694] [KO:K03945]
(MT-C1D) NDUFA11 [HSA:126328] [KO:K03956]
(MT-C1D) NDUFAF1 [HSA:51103] [KO:K18159]
(MT-C1D/LS) NDUFAF2 [HSA:91942] [KO:K18160]
(MT-C1D) NDUFAF3 [HSA:25915] [KO:K09008]
(MT-C1D) NDUFAF4 [HSA:29078] [KO:K18161]
(MT-C1D/LS) NDUFV1 [HSA:4723] [KO:K03942]
(MT-C1D) NDUFV2 [HSA:4729] [KO:K03943]
(MT-C1D) NUBPL [HSA:80224] [KO:K03593]
(MT-C1D/LS) FOXRED1 [HSA:55572] [KO:K18166]
(MT-C1D) NDUFAF5 [HSA:79133] [KO:K18162]
(MT-C1D/LS) NDUFAF6 [HSA:137682] [KO:K18163]
(MT-C1D) NDUFB3 [HSA:4709] [KO:K03959]
(MT-C1D) NDUFB9 [HSA:4715] [KO:K03965]
(MT-C1D) ACAD9 [HSA:28976] [KO:K15980]
(MT-C1D) TIMMDC1 [HSA:51300]
(MT-C1D) TMEM126B [HSA:55863] [KO:K18165]
(MT-C1D/LHON/LDYT/MELAS) MT-ND1 [HSA:4535] [KO:K03878]
(MT-C1D/LHON) MT-ND2 [HSA:4536] [KO:K03879]
(MT-C1D/LS/LDYT/KSS) MT-ND3 [HSA:4537] [KO:K03880]
(MT-C1D/LHON/LDYT/KSS) MT-ND4 [HSA:4538] [KO:K03881]
(MT-C1D/LHON) MT-ND4L [HSA:4539] [KO:K03882]
(MT-C1D/LHON/LS/MELAS/KSS) MT-ND5 [HSA:4540] [KO:K03883]
(MT-C1D/LHON/LDYT/KSS) MT-ND6 [HSA:4541] [KO:K03884]
(MT-C2D) SDHAF1 [HSA:644096] [KO:K18167]
(MT-C2D/LS) SDHA [HSA:6389] [KO:K00234]
(MT-C3D/LS/GRACILE) BCS1L [HSA:617] [KO:K08900]
(MT-C3D) UQCRQ [HSA:27089] [KO:K00418]
(MT-C3D) UQCRB [HSA:7381] [KO:K00417]
(MT-C3D/LHON/KSS) MT-CYB [HSA:4519] [KO:K00412]
(MT-C3D) TTC19 [HSA:54902] [KO:K18169]
(MT-C3D) UQCRC2 [HSA:7385] [KO:K00415]
(MT-C3D) CYC1 [HSA:1537] [KO:K00413]
(MT-C3D) UQCC2 [HSA:84300] [KO:K17682]
(MT-C3D) LYRM7 [HSA:90624] [KO:K18170]
(MT-C3D) UQCC3 [HSA:790955]
Drug
(MELAS) L-arginin [DR:D02982]
(MELAS) Coenzyme Q10 [DR:D01065]
Comment
KSS, LHON, MELAS, and MERRF can be caused by mutation in multiple genes encoded by the mitochondrial genome mtDNA.
Other DBs
Reference
  Authors
Distelmaier F, Koopman WJ, van den Heuvel LP, Rodenburg RJ, Mayatepek E, Willems PH, Smeitink JA
  Title
Mitochondrial complex I deficiency: from organelle dysfunction to clinical disease.
  Journal
Brain 132:833-42 (2009)
DOI:10.1093/brain/awp058
Reference
  Authors
Bayley JP, Devilee P, Taschner PE
  Title
The SDH mutation database: an online resource for succinate dehydrogenase sequence variants involved in pheochromocytoma, paraganglioma and mitochondrial complex II deficiency.
  Journal
BMC Med Genet 6:39 (2005)
DOI:10.1186/1471-2350-6-39
Reference
  Authors
Benit P, Lebon S, Rustin P
  Title
Respiratory-chain diseases related to complex III deficiency.
  Journal
Biochim Biophys Acta 1793:181-5 (2009)
DOI:10.1016/j.bbamcr.2008.06.004
Reference
  Authors
Saneto RP, Friedman SD, Shaw DW
  Title
Neuroimaging of mitochondrial disease.
  Journal
Mitochondrion 8:396-413 (2008)
DOI:10.1016/j.mito.2008.05.003
Reference
  Authors
Alfadhel M, Lillquist YP, Waters PJ, Sinclair G, Struys E, McFadden D, Hendson G, Hyams L, Shoffner J, Vallance HD
  Title
Infantile cardioencephalopathy due to a COX15 gene defect: report and review.
  Journal
Am J Med Genet A 155A:840-4 (2011)
DOI:10.1002/ajmg.a.33881
Reference
  Authors
Santa KM
  Title
Treatment options for mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome.
  Journal
Pharmacotherapy 30:1179-96 (2010)
DOI:10.1592/phco.30.11.1179
Reference
  Authors
Koga Y, Povalko N, Nishioka J, Katayama K, Kakimoto N, Matsuishi T
  Title
MELAS and L-arginine therapy: pathophysiology of stroke-like episodes.
  Journal
Ann N Y Acad Sci 1201:104-10 (2010)
DOI:10.1111/j.1749-6632.2010.05624.x
Reference
  Authors
Coskun P, Wyrembak J, Schriner S, Chen HW, Marciniack C, Laferla F, Wallace DC
  Title
A mitochondrial etiology of Alzheimer and Parkinson disease.
  Journal
Biochim Biophys Acta (2011)
DOI:10.1016/j.bbagen.2011.08.008
Reference
  Authors
He M, Rutledge SL, Kelly DR, Palmer CA, Murdoch G, Majumder N, Nicholls RD, Pei Z, Watkins PA, Vockley J
  Title
A new genetic disorder in mitochondrial fatty acid beta-oxidation: ACAD9 deficiency.
  Journal
Am J Hum Genet 81:87-103 (2007)
DOI:10.1086/519219
Reference
  Authors
Blazquez A, Gil-Borlado MC, Moran M, Verdu A, Cazorla-Calleja MR, Martin MA, Arenas J, Ugalde C
  Title
Infantile mitochondrial encephalomyopathy with unusual phenotype caused by a novel BCS1L mutation in an isolated complex III-deficient patient.
  Journal
Neuromuscul Disord 19:143-6 (2009)
DOI:10.1016/j.nmd.2008.11.016
Reference
  Authors
Miyake N, Yano S, Sakai C, Hatakeyama H, Matsushima Y, Shiina M, Watanabe Y, Bartley J, Abdenur JE, Wang RY, Chang R, Tsurusaki Y, Doi H, Nakashima M, Saitsu H, Ogata K, Goto Y, Matsumoto N
  Title
Mitochondrial complex III deficiency caused by a homozygous UQCRC2 mutation presenting with neonatal-onset recurrent metabolic decompensation.
  Journal
Hum Mutat 34:446-52 (2013)
DOI:10.1002/humu.22257
Reference
  Authors
Gaignard P, Menezes M, Schiff M, Bayot A, Rak M, Ogier de Baulny H, Su CH, Gilleron M, Lombes A, Abida H, Tzagoloff A, Riley L, Cooper ST, Mina K, Sivadorai P, Davis MR, Allcock RJ, Kresoje N, Laing NG, Thorburn DR, Slama A, Christodoulou J, Rustin P
  Title
Mutations in CYC1, encoding cytochrome c1 subunit of respiratory chain complex III, cause insulin-responsive hyperglycemia.
  Journal
Am J Hum Genet 93:384-9 (2013)
DOI:10.1016/j.ajhg.2013.06.015
Reference
  Authors
Tucker EJ, Wanschers BF, Szklarczyk R, Mountford HS, Wijeyeratne XW, van den Brand MA, Leenders AM, Rodenburg RJ, Reljic B, Compton AG, Frazier AE, Bruno DL, Christodoulou J, Endo H, Ryan MT, Nijtmans LG, Huynen MA, Thorburn DR
  Title
Mutations in the UQCC1-interacting protein, UQCC2, cause human complex III deficiency associated with perturbed cytochrome b protein expression.
  Journal
PLoS Genet 9:e1004034 (2013)
DOI:10.1371/journal.pgen.1004034
Reference
  Authors
Dallabona C, Abbink TE, Carrozzo R, Torraco A, Legati A, van Berkel CG, Niceta M, Langella T, Verrigni D, Rizza T, Diodato D, Piemonte F, Lamantea E, Fang M, Zhang J, Martinelli D, Bevivino E, Dionisi-Vici C, Vanderver A, Philip SG, Kurian MA, Verma IC, Bijarnia-Mahay S, Jacinto S, Furtado F, Accorsi P, Ardissone A, Moroni I, Ferrero I, Tartaglia M, Goffrini P, Ghezzi D, van der Knaap MS, Bertini E
  Title
LYRM7 mutations cause a multifocal cavitating leukoencephalopathy with distinct MRI appearance.
  Journal
Brain 139:782-94 (2016)
DOI:10.1093/brain/awv392
Reference
  Authors
Wanschers BF, Szklarczyk R, van den Brand MA, Jonckheere A, Suijskens J, Smeets R, Rodenburg RJ, Stephan K, Helland IB, Elkamil A, Rootwelt T, Ott M, van den Heuvel L, Nijtmans LG, Huynen MA
  Title
A mutation in the human CBP4 ortholog UQCC3 impairs complex III assembly, activity and cytochrome b stability.
  Journal
Hum Mol Genet 23:6356-65 (2014)
DOI:10.1093/hmg/ddu357
Reference
  Authors
Fassone E, Taanman JW, Hargreaves IP, Sebire NJ, Cleary MA, Burch M, Rahman S
  Title
Mutations in the mitochondrial complex I assembly factor NDUFAF1 cause fatal infantile hypertrophic cardiomyopathy.
  Journal
J Med Genet 48:691-7 (2011)
DOI:10.1136/jmedgenet-2011-100340
Reference
  Authors
Calvo SE, Compton AG, Hershman SG, Lim SC, Lieber DS, Tucker EJ, Laskowski A, Garone C, Liu S, Jaffe DB, Christodoulou J, Fletcher JM, Bruno DL, Goldblatt J, Dimauro S, Thorburn DR, Mootha VK
  Title
Molecular diagnosis of infantile mitochondrial disease with targeted next-generation sequencing.
  Journal
Sci Transl Med 4:118ra10 (2012)
DOI:10.1126/scitranslmed.3003310
Reference
  Authors
Haack TB, Haberberger B, Frisch EM, Wieland T, Iuso A, Gorza M, Strecker V, Graf E, Mayr JA, Herberg U, Hennermann JB, Klopstock T, Kuhn KA, Ahting U, Sperl W, Wilichowski E, Hoffmann GF, Tesarova M, Hansikova H, Zeman J, Plecko B, Zeviani M, Wittig I, Strom TM, Schuelke M, Freisinger P, Meitinger T, Prokisch H
  Title
Molecular diagnosis in mitochondrial complex I deficiency using exome sequencing.
  Journal
J Med Genet 49:277-83 (2012)
DOI:10.1136/jmedgenet-2012-100846

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