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Pathway Description
Maple Syrup Urine Disease
Homo sapiens
Disease Pathway
Maple syrup urine disease, also called BCKD deficiency, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder caused by a defective BCKDHA, BKCDHB or DBT gene. These genes code for a protein which is vital in the breakdown of amino acids, specifically the amino acids leucine, isoleucine and valine. This disorder is characterized by a large accumulation of these amino acids in the body. Symptoms of the disorder include a distinct maple syrup smell of the urine, vomiting, lethargy, abnormal movements and delayed development. Treatment includes long-term dietary management which aims to restrict the consumption of branched-chain amino acids. It is estimated that maple syrup urine disorder affects 1 in 185,000 infants globally. This number increases significantly when looking specifically at Old World Order Mennonites, where the prevalence is 1 in 380 infants.
References
Maple Syrup Urine Disease References
[Uniprot: P12694](http://www.uniprot.org/uniprot/P12694)
[Uniprot: P21953](http://www.uniprot.org/uniprot/P21953)
[Uniprot: P09622](http://www.uniprot.org/uniprot/P09622)
[OMIM: Entry 248600](http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=248600)
Hommes, F., Van den Berg, C. Inborn Errors of Metabolism. (1973) p. 337. London: Academic Press.
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.65 Heilbronn: SPS Verlagsgesellschaft
Chuang JL, Fisher CR, Cox RP, Chuang DT: Molecular basis of maple syrup urine disease: novel mutations at the E1 alpha locus that impair E1(alpha 2 beta 2) assembly or decrease steady-state E1 alpha mRNA levels of branched-chain alpha-keto acid dehydrogenase complex. Am J Hum Genet. 1994 Aug;55(2):297-304.
Pubmed: 8037208
Chuang JL, Wynn RM, Moss CC, Song JL, Li J, Awad N, Mandel H, Chuang DT: Structural and biochemical basis for novel mutations in homozygous Israeli maple syrup urine disease patients: a proposed mechanism for the thiamin-responsive phenotype. J Biol Chem. 2004 Apr 23;279(17):17792-800. doi: 10.1074/jbc.M313879200. Epub 2004 Jan 23.
Pubmed: 14742428
Danner DJ, Armstrong N, Heffelfinger SC, Sewell ET, Priest JH, Elsas LJ: Absence of branched chain acyl-transferase as a cause of maple syrup urine disease. J Clin Invest. 1985 Mar;75(3):858-60. doi: 10.1172/JCI111783.
Pubmed: 3980729
Edelmann L, Wasserstein MP, Kornreich R, Sansaricq C, Snyderman SE, Diaz GA: Maple syrup urine disease: identification and carrier-frequency determination of a novel founder mutation in the Ashkenazi Jewish population. Am J Hum Genet. 2001 Oct;69(4):863-8. doi: 10.1086/323677. Epub 2001 Aug 16.
Pubmed: 11509994
Frezal J, Amedee-Manesme O, Mitchell G, Heuertz S, Rey F, Rey J, Saudubray JM: Maple syrup urine disease: two different forms within a single family. Hum Genet. 1985;71(1):89-91.
Pubmed: 4029957
Blackburn PR, Gass JM, Vairo FPE, Farnham KM, Atwal HK, Macklin S, Klee EW, Atwal PS: Maple syrup urine disease: mechanisms and management. Appl Clin Genet. 2017 Sep 6;10:57-66. doi: 10.2147/TACG.S125962. eCollection 2017.
Pubmed: 28919799
Valine, Leucine, and Isoleucine Degradation References
Lehninger, A.L. Lehninger principles of biochemistry (4th ed.) (2005). New York: W.H Freeman.
Salway, J.G. Metabolism at a glance (3rd ed.) (2004). Alden, Mass.: Blackwell Pub.
Wanders RJ, Duran M, Loupatty FJ: Enzymology of the branched-chain amino acid oxidation disorders: the valine pathway. J Inherit Metab Dis. 2012 Jan;35(1):5-12. doi: 10.1007/s10545-010-9236-x. Epub 2010 Nov 23.
Pubmed: 21104317
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