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Pathway Description
Ethylmalonic Encephalopathy
Homo sapiens
Disease Pathway
Ethylmalonic Encephalopathy (Epema Syndrome; EE) is a rare autosomal recessive disorder caused by a mutation in the ETHE1 gene which codes for protein ETHE1. A deficiency of this protein inhibits proper energy production in mitochondria and a deficiency in cytochrome c oxidase. This results in accumulation of 2-methylbutyrylglycine, N-butyrylglycine, isobutyrylglycine, isovalerylglycine, and methylsuccinic acid in urine. Concentrations of L-carnitine are reduced in plasma. Symptoms, which present at birth, include peripheral neuropathy, seizures, microcephaly, and hypotonia lead to premature death. Treatment includes riboflavin and L-carnitine.
References
Ethylmalonic Encephalopathy References
[Wikipedia: Ethylmalonic encephalopathy](http://en.wikipedia.org/wiki/Ethylmalonic_encephalopathy)
[Uniprot: O95571](http://www.uniprot.org/uniprot/O95571)
[OMIM: Entry 602473](http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602473)
Engelke, U., van der Graaf, M., Heerschap, A., Hoenderop, S., Moolenaar, S., Morava, E., Wevers, R. Handbook of 1H-NMR spectroscopy in inborn errors of metabolism: body fluid NMR spectroscopy and in vivo MR spectroscopy (2nd ed) (2007) p.38 Heilbronn: SPS Verlagsgesellschaft
Burlina A, Zacchello F, Dionisi-Vici C, Bertini E, Sabetta G, Bennet MJ, Hale DE, Schmidt-Sommerfeld E, Rinaldo P: New clinical phenotype of branched-chain acyl-CoA oxidation defect. Lancet. 1991 Dec 14;338(8781):1522-3.
Pubmed: 1683940
Grosso S, Mostardini R, Farnetani MA, Molinelli M, Berardi R, Dionisi-Vici C, Rizzo C, Morgese G, Balestri P: Ethylmalonic encephalopathy: further clinical and neuroradiological characterization. J Neurol. 2002 Oct;249(10):1446-50. doi: 10.1007/s00415-002-0880-4.
Pubmed: 12382164
Mineri R, Rimoldi M, Burlina AB, Koskull S, Perletti C, Heese B, von Dobeln U, Mereghetti P, Di Meo I, Invernizzi F, Zeviani M, Uziel G, Tiranti V: Identification of new mutations in the ETHE1 gene in a cohort of 14 patients presenting with ethylmalonic encephalopathy. J Med Genet. 2008 Jul;45(7):473-8. doi: 10.1136/jmg.2008.058271.
Pubmed: 18593870
Ozand PT, Rashed M, Millington DS, Sakati N, Hazzaa S, Rahbeeni Z, al Odaib A, Youssef N, Mazrou A, Gascon GG, et al.: Ethylmalonic aciduria: an organic acidemia with CNS involvement and vasculopathy. Brain Dev. 1994 Nov;16 Suppl:12-22.
Pubmed: 7726376
Tiranti V, D'Adamo P, Briem E, Ferrari G, Mineri R, Lamantea E, Mandel H, Balestri P, Garcia-Silva MT, Vollmer B, Rinaldo P, Hahn SH, Leonard J, Rahman S, Dionisi-Vici C, Garavaglia B, Gasparini P, Zeviani M: Ethylmalonic encephalopathy is caused by mutations in ETHE1, a gene encoding a mitochondrial matrix protein. Am J Hum Genet. 2004 Feb;74(2):239-52. doi: 10.1086/381653. Epub 2004 Jan 19.
Pubmed: 14732903
Di Meo I, Lamperti C, Tiranti V: Ethylmalonic Encephalopathy
Pubmed: 28933811
Di Meo I, Auricchio A, Lamperti C, Burlina A, Viscomi C, Zeviani M: Effective AAV-mediated gene therapy in a mouse model of ethylmalonic encephalopathy. EMBO Mol Med. 2012 Sep;4(9):1008-14. doi: 10.1002/emmm.201201433. Epub 2012 Aug 20.
Pubmed: 22903887
Fatty Acid Metabolism References
Lehninger, A.L. Lehninger principles of biochemistry (4th ed.) (2005). New York: W.H Freeman.
Lodish, H. et al. Molecular cell biology. (2004) New York: W.H Freeman.
Salway, J.G. Metabolism at a glance (3rd ed.) (2004). Alden, Mass.: Blackwell Pub.
Vance, D.E., and Vance, J.E. Biochemistry of lipids, lipoproteins, and membranes (4th ed.) (2002) Amsterdam; Boston: Elsevier.
Wakil SJ, Abu-Elheiga LA: Fatty acid metabolism: target for metabolic syndrome. J Lipid Res. 2009 Apr;50 Suppl:S138-43. doi: 10.1194/jlr.R800079-JLR200. Epub 2008 Dec 1.
Pubmed: 19047759
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