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Maple Syrup Urine Disease Workup

  • Author: Olaf A Bodamer, MD, PhD, FAAP, FACMG; Chief Editor: Luis O Rohena, MD  more...
Updated: Nov 04, 2014

Laboratory Studies

Plasma amino acids should be evaluated to assess the elevation of branched-chain amino acids and to detect alloisoleucine. The detection of alloisoleucine is diagnostic for maple syrup urine disease (MSUD). Alloisoleucine may not appear until the sixth day of life, even when leucine levels are elevated. Transient elevations of branched-chain amino acids (without the presence of alloisoleucine) may develop in patients with ketotic hypoglycemia and in patients in the postabsorptive state. Plasma amino acid levels may also be artificially elevated in infants on total parental nutrition (TPN).

Urine organic acids should be analyzed using gas chromatography-mass spectrometry (GC-MS) to detect alpha-hydroxyisovalerate, lactate, pyruvate, and alpha-ketoglutarate. A random urine specimen is usually sufficient.

Newborn screening for MSUD is performed with tandem mass spectrometry using concentrations of leucine and isoleucine and the Fisher Ratio (branch-chain amino acids/phenylalanine and tyrosine) as diagnostic measures. Immediate treatment should follow the identification of affected newborn infants.

Enzyme activity can be measured in lymphocytes, cultured fibroblasts, or both, although this test is not required for diagnosis.

Molecular testing is available for the three genes that have been reported in patients with MSUD, namely for BCKDHA encoding BCKA decarboxylase (E1) alpha subunit gene (MSUD type 1A), BCKDHB encoding BCKA decarboxylase (E1) beta subunit gene (MSUD type 1B), and DBT encoding dihydrolipoyl transacylase (E2) subunit gene (MSUD type 2) (see also GeneTests).

Molecular confirmation should be sought in any patient with MSUD to confirm the diagnosis, to provide additional information about prognosis, to provide the basis for in-depth genetic counseling for the family, and to provide the basis for prenatal testing.

Prenatal diagnosis can be performed by measuring enzyme activity in cultured amniocytes or chorion villus cells, mutation analysis, or by measuring branch-chain amino acid concentrations in amniotic fluid. However, molecular analysis is the most reliable and therefore preferred method for prenatal diagnosis. An important prerequisite is the identification of two pathogenic mutations in the index patient.

Contributor Information and Disclosures

Olaf A Bodamer, MD, PhD, FAAP, FACMG Park Gerald Chair in Genetics and Genomics, Associate Chief, Division of Genetics and Genomics, Department of Medicine, Boston Children's Hospital, Harvard Medical School

Olaf A Bodamer, MD, PhD, FAAP, FACMG is a member of the following medical societies: American Medical Association, American Society of Human Genetics

Disclosure: Nothing to disclose.


Brendan Lee, MD, PhD Professor, Robert and Janice McNair Endowed Chair in Molecular and Human Genetics, Department of Molecular and Human Genetics, Baylor College of Medicine

Brendan Lee, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics, Society for Pediatric Research

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Biomarin; Retrophin;.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Lois J Starr, MD, FAAP Assistant Professor of Pediatrics, Clinical Geneticist, Munroe Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center

Lois J Starr, MD, FAAP is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics

Disclosure: Nothing to disclose.

Chief Editor

Luis O Rohena, MD Chief, Medical Genetics, San Antonio Military Medical Center; Assistant Professor of Pediatrics, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Assistant Professor of Pediatrics, University of Texas Health Science Center at San Antonio

Luis O Rohena, MD is a member of the following medical societies: American Academy of Pediatrics, American Chemical Society, American College of Medical Genetics and Genomics, American Society of Human Genetics

Disclosure: Nothing to disclose.

Additional Contributors

Christian J Renner, MD Consulting Staff, Department of Pediatrics, University Hospital for Children and Adolescents, Erlangen, Germany

Disclosure: Nothing to disclose.

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