Maple Syrup Urine Disease


Maple Syrup Urine Disease (Branched-chain alpha-keto acid dehydrogenase deficiency, MSUD) is caused by a deficiency of the branched-chain alpha-keto acid dehydrogenase enzyme complex (BCKDH), which normally degrades the branched chain amino acids leucine, isoleucine, and valine. The disease is characterized in an infant by the presence of sweet-smelling urine, with an odor similar to that of maple syrup. Increased amounts of valine, leucine and isoleucine and their toxic byproducts accumulate in the blood, plasma, and urine. Symptoms include ataxia, encephalopathy, ketosis, mental retardation, seizures, and a maple syrup or caramel odor.

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References

  1. Uniprot: P12694
  2. Uniprot: P21953
  3. Uniprot: P09622
  4. OMIM: Entry 248600
  5. Hommes, F., Van den Berg, C. (1973). Inborn Errors of Metabolism (pp. 337). London: Academic Press.
  6. 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 68) (2nd ed). Heilbronn: SPS Verlagsgesellschaft
  7. 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 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
  8. 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. Epub 2004 Jan 23. Pubmed
  9. 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. Pubmed
  10. 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. Epub 2001 Aug 16. Pubmed
  11. 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