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Pathway Description
Leigh Syndrome
Homo sapiens
Category:
Metabolite Pathway
Sub-Category:
Disease
Created: 2013-08-01
Last Updated: 2022-12-12
Leigh Syndrome, also called Leigh Disease or infantile subacute necrotizing encephalopathy, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder that is caused by a mutation of any one of 75 different genes. Disruptions of the complexes I or IV are the most common reasons for Leigh syndrome. Complex IV is crucial in the electron transfer steps of oxidative phosphorylation, which is needed to provide energy to the mitochondria. This disorder is characterized by a large accumulation of lactate in the body. Symptoms of the disorder include diarrhea, dysphagia and vomiting. There is no cure for Leigh syndrome and the loss motor skills degenerate rapidly. It is estimated that Leigh syndrome affects 1 in 40,000 individuals.
References
Leigh Syndrome References
[Wikipedia: Leigh%27s disease](http://en.wikipedia.org/wiki/Leigh%27s_disease)
[OMIM: Entry 256000](http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=256000)
[Uniprot: P08559](http://www.uniprot.org/uniprot/P08559)
[Uniprot: P00846](http://www.uniprot.org/uniprot/P00846)
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Pubmed: 5457539
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Pubmed: 8687192
Kretzschmar HA, DeArmond SJ, Koch TK, Patel MS, Newth CJ, Schmidt KA, Packman S: Pyruvate dehydrogenase complex deficiency as a cause of subacute necrotizing encephalopathy (Leigh disease). Pediatrics. 1987 Mar;79(3):370-3.
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Pubmed: 25978847
Pyruvate Metabolism References
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Salway, J.G. Metabolism at a glance (3rd ed.) (2004). Alden, Mass.: Blackwell Pub.
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Pubmed: 24363178
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Pubmed: 7918683
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Pubmed: 14702039
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Pubmed: 18351441
Kanno H, Fujii H, Hirono A, Miwa S: cDNA cloning of human R-type pyruvate kinase and identification of a single amino acid substitution (Thr384----Met) affecting enzymatic stability in a pyruvate kinase variant (PK Tokyo) associated with hereditary hemolytic anemia. Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):8218-21. doi: 10.1073/pnas.88.18.8218.
Pubmed: 1896471
Tani K, Fujii H, Nagata S, Miwa S: Human liver type pyruvate kinase: complete amino acid sequence and the expression in mammalian cells. Proc Natl Acad Sci U S A. 1988 Mar;85(6):1792-5. doi: 10.1073/pnas.85.6.1792.
Pubmed: 3126495
Kanno H, Fujii H, Miwa S: Structural analysis of human pyruvate kinase L-gene and identification of the promoter activity in erythroid cells. Biochem Biophys Res Commun. 1992 Oct 30;188(2):516-23. doi: 10.1016/0006-291x(92)91086-6.
Pubmed: 1445295
Stoffel M, Xiang KS, Espinosa R 3rd, Cox NJ, Le Beau MM, Bell GI: cDNA sequence and localization of polymorphic human cytosolic phosphoenolpyruvate carboxykinase gene (PCK1) to chromosome 20, band q13.31: PCK1 is not tightly linked to maturity-onset diabetes of the young. Hum Mol Genet. 1993 Jan;2(1):1-4. doi: 10.1093/hmg/2.1.1.
Pubmed: 8490617
Ting CN, Burgess DL, Chamberlain JS, Keith TP, Falls K, Meisler MH: Phosphoenolpyruvate carboxykinase (GTP): characterization of the human PCK1 gene and localization distal to MODY on chromosome 20. Genomics. 1993 Jun;16(3):698-706. doi: 10.1006/geno.1993.1250.
Pubmed: 8325643
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Pubmed: 21726808
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Pubmed: 8786100
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Pubmed: 15815621
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Pubmed: 1993674
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Pubmed: 11401430
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Pubmed: 12127981
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Pubmed: 15489334
Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22.
Pubmed: 24275569
Cordell PA, Futers TS, Grant PJ, Pease RJ: The Human hydroxyacylglutathione hydrolase (HAGH) gene encodes both cytosolic and mitochondrial forms of glyoxalase II. J Biol Chem. 2004 Jul 2;279(27):28653-61. doi: 10.1074/jbc.M403470200. Epub 2004 Apr 26.
Pubmed: 15117945
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Pubmed: 11157797
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Pubmed: 7684374
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Pubmed: 8670058
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