Cerebral Edema in Maple Syrup Urine Disease Despite Newborn Screening Diagnosis and Early Initiation of Treatment

  • Kenneth A. Myers
  • Melanie Reeves
  • Xing-Chang Wei
  • Aneal Khan
Case Report
Part of the JIMD Reports book series (JIMD, volume 3)


A 7-day-old girl had an elevated leucine level on newborn screen drawn at 2 days of age and was suspected of having maple syrup urine disease (MSUD). When reported, the patient was immediately admitted to hospital, and started on a modified diet involving high calories with reduced branched chain amino acid (BCAA) formula. Clinical exam was normal at initial assessment. Despite rapid initiation of treatment, the baby became lethargic and somnolent over the next day. Diet was stopped and infusions of 12.5% dextrose and 20% intravenous lipids at 2 g/kg per day were immediately started. Lethargy improved within 3 h of intravenous therapy initiation. Brain magnetic resonance imaging demonstrated diffuse cerebral edema, and symmetric restricted diffusion in bilateral cerebellar white matter, dorsal brainstem, thalami, globi pallidi, posterior limbs of internal capsules, and corona radiata. Plasma leucine was 1.98 mmol/L on admission (normal 0.05–0.17 mmol/L), decreasing to 1.34 mmol/L with diet, however clinical deterioration occurred despite improving leucine levels.

Cerebral edema in MSUD is thought secondary to a combination of increased cerebral BCAA levels, and depleted levels of other essential amino acids, as well as neurotransmitters. Our case illustrates that newborns can develop encephalopathy with cerebral edema despite treatment with special formula initiated while asymptomatic. These findings suggest decompensation may begin early on, so that early introduction of high dextrose infusion and intravenous lipids, in combination with reduced BCAA formula, should be initiated for any patient with a positive newborn screen for MSUD.


  1. Brismar J, Aqeel A, Brismar G et al (1990) Maple syrup urine disease: findings on CT and MR scans of the brain in 10 infants. AJNR Am J Neuroradiol 11:1219–1228PubMedGoogle Scholar
  2. Cavalleri F, Berardi A, Burlina AB et al (2002) Diffusion-weighted MRI of maple syrup urine disease encephalopathy. Neuroradiology 44:499–502PubMedCrossRefGoogle Scholar
  3. Ferraz-Filho JR, Floriano VH, Quirici MB et al (2009) Contribution of the diffusion-weighted MRI in the diagnosis and follow-up of encephalopathy caused by maple syrup urine disease in a full-term newborn. Arq Neuropsiquiatr 67:719–723PubMedCrossRefGoogle Scholar
  4. Jan W, Zimmerman RA, Wang ZJ et al (2003) MR diffusion imaging and MR spectroscopy of maple syrup urine disease during acute metabolic decompensation. Neuroradiology 45:393–399PubMedCrossRefGoogle Scholar
  5. Patel MS, Auerbach VH, Grover WD et al (1973) Effect of the branched-chain alpha-keto acids on pyruvate metabolism by homogenates of human brain. J Neurochem 20:1793–1796PubMedCrossRefGoogle Scholar
  6. Sakai M, Inoue Y, Oba H et al (2005) Age dependence of diffusion-weighted magnetic resonance imaging findings in maple syrup urine disease encephalopathy. J Comput Assist Tomogr 29:524–527PubMedCrossRefGoogle Scholar
  7. Sener RN (2007) Maple syrup urine disease: diffusion MRI, and proton MR spectroscopy findings. Comput Med Imaging Graph 31:106–110PubMedCrossRefGoogle Scholar
  8. Sgaravatti AM, Rosa RB, Schuck PF et al (2003) Inhibition of brain energy metabolism by the alpha-keto acids accumulating in maple syrup urine disease. Biochim Biophys Acta 1639:232–238PubMedCrossRefGoogle Scholar
  9. Strauss KA, Wardley B, Robinson D et al (2010) Classical maple syrup urine disease and brain development: principles of management and formula design. Mol Genet Metab 99:333–345PubMedCrossRefGoogle Scholar
  10. Zinnanti WJ, Lazovic J, Griffin K et al (2009) Dual mechanism of brain injury and novel treatment strategy in maple syrup urine disease. Brain 132:903–918PubMedCrossRefGoogle Scholar

Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Kenneth A. Myers
    • 1
  • Melanie Reeves
    • 2
  • Xing-Chang Wei
    • 3
  • Aneal Khan
    • 4
  1. 1.Department of Pediatrics, Division of Neurology, Alberta Children’s HospitalUniversity of CalgaryCalgaryCanada
  2. 2.Alberta Children’s Hospital, Metabolic Diseases ClinicCalgaryCanada
  3. 3.Diagnostic ImagingAlberta Children’s HospitalCalgaryCanada
  4. 4.Department of Pediatrics and Medical Genetics, Alberta Children’s HospitalUniversity of CalgaryCalgaryCanada

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