Ethylmalonic Encephalopathy


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.

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References

  1. Wikipedia: Ethylmalonic encephalopathy
  2. Uniprot: O95571
  3. OMIM: Entry 602473
  4. Engelke, U., van der Graaf, M., Heerschap, A., Hoenderop, S., Moolenaar, S., Morava, E., Wevers, R. (2007). Handbook of 1H-NMR spectroscopy in inborn errors of metabolism: body fluid NMR spectroscopy and in vivo MR spectroscopy (pp 41) (2nd ed). Heilbronn: SPS Verlagsgesellschaft
  5. 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
  6. 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. Pubmed
  7. 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. Pubmed
  8. 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
  9. 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. Epub 2004 Jan 19. Pubmed