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GTR Home > Conditions/Phenotypes > Maple syrup urine disease


Excerpted from the GeneReview: Maple Syrup Urine Disease
Maple syrup urine disease (MSUD) is categorized as classic (severe), intermediate, or intermittent. Neonates with classic MSUD are born asymptomatic but without treatment follow a predictable course: 12–24 hours. Elevated concentrations of branched-chain amino acids (BCAAs; leucine, isoleucine, and valine) and alloisoleucine, as well as a generalized disturbance of amino acid concentration ratios, are present in blood and the maple syrup odor can be detected in cerumen; Two to three days. Early and nonspecific signs of metabolic intoxication (i.e., irritability, hypersomnolence, anorexia) are accompanied by the presence of branched-chain alpha-ketoacids, acetoacetate, and beta-hydroxybutyrate in urine; Four to six days. Worsening encephalopathy manifests as lethargy, apnea, opisthotonos, and reflexive "fencing" or "bicycling" movements as the sweet maple syrup odor becomes apparent in urine; Seven to ten days. Severe intoxication culminates in critical cerebral edema, coma, and central respiratory failure. Individuals with intermediate MSUD have partial branched-chain alpha-ketoacid dehydrogenase deficiency that manifests only intermittently or responds to dietary thiamine therapy; these individuals can experience severe metabolic intoxication and encephalopathy in the face of sufficient catabolic stress. In the era of newborn screening (NBS), the prompt initiation of treatment of asymptomatic infants detected by NBS means that most individuals who would have developed neonatal manifestations of MSUD remain asymptomatic with continued treatment adherence.

Genes See tests for all associated and related genes

  • Also known as: BCKDE1A, MSU, MSUD1, MSUD1A, OVD1A, BCKDHA
    Summary: branched chain keto acid dehydrogenase E1 subunit alpha

  • Also known as: BCKDE1B, BCKDH E1-beta, E1B, MSUD1B, OVD1B, BCKDHB
    Summary: branched chain keto acid dehydrogenase E1 subunit beta

Practice guidelines

  • ACMG ACT, 2021
    American College of Medical Genetics and Genomics, Newborn Screening ACT Sheet, Increased Leucine, Maple Syrup Urine Disease, 2021
  • ACMG Algorithm, 2021
    American College of Medical Genetics and Genomics, Algorithm, Leucine Elevated, 2021
  • GMDI/SERN, 2021
    MSUD Nutrition Management Guidelines
  • ACMG ACT, 2011
    American College of Medical Genetics ACT Sheet, Carrier Screening ACT Sheet Ashkenazi Jewish Genetic Disorders

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