eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Metabolic Diseases

Maple Syrup Urine Disease: Treatment & Medication

Author: Olaf A Bodamer, MD, PhD, FACMG, Professor, Department of Pediatrics, Biochemical Genetics and Neonatal Screening Laboratories, University of Vienna Children's Hospital, Austria
Coauthor(s): Brendan Lee, MD, PhD, Associate Professor, Department of Molecular and Human Genetics, Baylor College of Medicine
Contributor Information and Disclosures

Updated: Jul 7, 2008

Treatment

Medical Care

The 2 main aspects to the treatment of maple syrup urine disease (MSUD) are long-term management and the treatment of episodes of acute metabolic decompensation. The mainstay in the treatment of MSUD is dietary restriction of branched-chain amino acids.

  • Aggressively treat episodes of metabolic decompensation. Initiate intravenous glucose infusions (5-8 mg/kg/min for infants) as rapidly as possible. Insulin infusions may be added to promote anabolism. Stop intake of branched-chain amino acids but resume intake as soon as plasma branched-chain amino acids normalize. Whenever possible, continue additional dietary support, including lipids and/or formulas free of branched-chain amino acid. In rare circumstances, hemodialysis or peritoneal dialysis is required to remove branched-chain amino acids and keto acids.
  • Three successful liver transplants in patients with classic MSUD have been reported.6 However, consider the risks and potential long-term complications of liver transplantation in contrast to the beneficial low-risk dietary therapy that has equally good outcome.
  • Initial studies using retroviral vectors to infect MSUD lymphocytes have shown stable correction of the enzyme deficiency. However, human gene therapy trials for MSUD remain to be performed.
  • Several successful pregnancies in patients with MSUD have been reported. The most critical period seems to be the immediate postpartum period. Take particular care to counteract catabolism during this time.

Diet

The goal of dietary therapy is normalization of branched-chain amino acids (particularly of leucine) by restricting intake of branched-chain amino acids without impairing growth and intellectual development. Dietary therapy must be lifelong. Several commercially available formulas and foods are available without branched-chain amino acids or with reduced levels of branched-chain amino acids.

Products are available for juveniles and adults, such as MSUD Express. The intake of leucine is calculated on an individual basis following the measurement of plasma branched-chain amino acids. Measure plasma amino acid levels on a regular basis at appropriate intervals for the first 6-12 months of life. In addition to dietary therapy, administer thiamine (10-20 mg/d) for 4 weeks to determine thiamine responsiveness.

Activity

Do not restrict activity.

Medication

Vitamins

Vitamins are organic substances required by the body in small amounts for various metabolic processes. Vitamins may be synthesized in small or insufficient amounts in the body or not synthesized at all, thus requiring supplementation. Administer thiamine in cases of thiamine-responsiveness.


Thiamine (Thiamilate)

An essential coenzyme in carbohydrate and amino acid metabolism. Combines with ATP to form thiamine pyrophosphate. PO absorption is poor, but parenteral route may be associated with severe adverse reactions.

Adult

10-20 mg/d PO divided tid; not to exceed 300 mg/d

Pediatric

10-20 mg/d PO divided tid for 2 wk, then 5-10 mg/d for 1 mo followed by reassessment of response; not to exceed 50 mg/d
10-25 mg/d IV/IM for limited time (<1 wk), then change to PO

IV dextrose solutions increase thiamine requirement; may enhance the effects of neuromuscular blocking agents

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

Pregnancy category C if dose exceeds RDA; sensitivity reactions can occur (intradermal test-dose recommended in suspected sensitivity); deaths have resulted from IV use

More on Maple Syrup Urine Disease

Overview: Maple Syrup Urine Disease
Differential Diagnoses & Workup: Maple Syrup Urine Disease
Treatment & Medication: Maple Syrup Urine Disease
Follow-up: Maple Syrup Urine Disease
References
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References

  1. Menkes JH, Hurst PL, Craig JM. A new syndrome: progressive familial infantile cerebral dysfunction associated with an unusual urinary substance. Pediatrics. Nov 1954;14(5):462-7. [Medline].

  2. Chuang DT. Maple syrup urine disease: it has come a long way. J Pediatr. Mar 1998;132(3 Pt 2):S17-23. [Medline].

  3. Dancis J, Levits M, Westall RG. Maple syrup urine disease: branched-chain keto-aciduria. Pediatrics. Jan 1960;25:72-9. [Medline].

  4. Snyderman SE, Norton PM, Roitman E, Holt LE Jr. Maple syrup urine disease, with particular reference to dietotherapy. Pediatrics. Oct 1964;34:454-72. [Medline].

  5. Scriver CR, Mackenzie S, Clow CL, Delvin E. Thiamine-responsive maple-syrup-urine disease. Lancet. Feb 13 1971;1(7694):310-2. [Medline].

  6. Wendel U, Saudubray JM, Bodner A, Schadewaldt P. Liver transplantation in maple syrup urine disease. Eur J Pediatr. Dec 1999;158 Suppl 2:S60-4. [Medline].

  7. Chuang DT, Shih VE. Maple syrup urine disease. In: Scriver CR, Beaudet AL, Valle DL, Sly WS, eds. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. New York, NY: McGraw-Hill Co; 2000.

  8. Fernstrom JD. Branched-chain amino acids and brain function. J Nutr. Jun 2005;135(6 Suppl):1539S-46S. [Medline].

  9. Hallam P, Lilburn M, Lee PJ. A new protein substitute for adolescents and adults with maple syrup urine disease (MSUD). J Inherit Metab Dis. 2005;28(5):665-72. [Medline].

  10. Harris RA, Joshi M, Jeoung NH, Obayashi M. Overview of the molecular and biochemical basis of branched-chain amino acid catabolism. J Nutr. Jun 2005;135(6 Suppl):1527S-30S. [Medline].

  11. Heldt K, Schwahn B, Marquardt I, et al. Diagnosis of MSUD by newborn screening allows early intervention without extraneous detoxification. Mol Genet Metab. Apr 2005;84(4):313-6. [Medline].

  12. Henneke M, Flaschker N, Helbling C, et al. Identification of twelve novel mutations in patients with classic and variant forms of maple syrup urine disease. Hum Mutat. Nov 2003;22(5):417. [Medline].

  13. Hoffmann B, Helbling C, Schadewaldt P, Wendel U. Impact of longitudinal plasma leucine levels on the intellectual outcome in patients with classic MSUD. Pediatr Res. Jan 2006;59(1):17-20. [Medline].

  14. Hoffmann GF, von Kries R, Klose D, et al. Frequencies of inherited organic acidurias and disorders of mitochondrial fatty acid transport and oxidation in Germany. Eur J Pediatr. Feb 2004;163(2):76-80. [Medline].

  15. Mitsubuchi H, Owada M, Endo F. Markers associated with inborn errors of metabolism of branched-chain amino acids and their relevance to upper levels of intake in healthy people: an implication from clinical and molecular investigations on maple syrup urine disease. J Nutr. Jun 2005;135(6 Suppl):1565S-70S. [Medline].

  16. Morton DH, Strauss KA, Robinson DL, et al. Diagnosis and treatment of maple syrup disease: a study of 36 patients. Pediatrics. Jun 2002;109(6):999-1008. [Medline].

  17. Righini A, Ramenghi LA, Parini R, et al. Water apparent diffusion coefficient and T2 changes in the acute stage of maple syrup urine disease: evidence of intramyelinic and vasogenic-interstitial edema. J Neuroimaging. Apr 2003;13(2):162-5. [Medline].

  18. Yudkoff M, Daikhin Y, Nissim I, et al. Brain amino acid requirements and toxicity: the example of leucine. J Nutr. Jun 2005;135(6 Suppl):1531S-8S. [Medline].

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Further Reading

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Keywords

maple syrup urine disease, MSUD, maple sugar urine disease, branched-chain ketonuria, branched chain ketonuria, branched-chain ketoaciduria, branched chain ketoaciduria, muscular hypotonia, muscular hypertonia, dystonia, seizures, encephalopathy, pseudotumor cerebri, pancreatitis, ketosis, otitis media, thiamine-responsive MSUD, ketotic hypoglycemia

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Contributor Information and Disclosures

Author

Olaf A Bodamer, MD, PhD, FACMG, Professor, Department of Pediatrics, Biochemical Genetics and Neonatal Screening Laboratories, University of Vienna Children's Hospital, Austria
Olaf A Bodamer, MD, PhD, FACMG is a member of the following medical societies: American Society of Human Genetics
Disclosure: Nothing to disclose.

Coauthor(s)

Brendan Lee, MD, PhD, Associate Professor, 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 Society for Pediatric Research
Disclosure: Hyperion Grant/research funds clinical research

Medical Editor

Christian J Renner, MD, Consulting Staff, Department of Pediatrics, University Hospital for Children and Adolescents, Erlangen, Germany
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

Leonard G Feld, MD, PhD, MMM, Chairman of Pediatrics, Carolinas Medical Center; Chief Medical Officer, Levine Children's Hospital, Carolinas Healthcare System
Leonard G Feld, MD, PhD, MMM is a member of the following medical societies: American Academy of Pediatrics, American College of Physician Executives, American Society of Nephrology, American Society of Pediatric Nephrology, International Society of Nephrology, and Juvenile Diabetes Foundation International
Disclosure: Nothing to disclose.

CME Editor

Paul D Petry, DO, FACOP, FAAP, Consulting Staff, Freeman Pediatric Care, Freeman Health System
Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association
Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD, Professor, Department of Pediatrics, Pathology and Microbiology, Executive Director, Hattie B Munroe Center for Human Genetics and Rehabilitation, University of Nebraska Medical Center
Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association
Disclosure: Nothing to disclose.

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