Maple Syrup Urine Disease Treatment & Management

  • Author: Olaf A Bodamer, MD, PhD, FACMG; Chief Editor: Bruce Buehler, MD   more...
 
Updated: Jan 18, 2012
 

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.[7] Children in a different study realized a high rate of patient and graft survival with normal liver function in all patients. The patients who were mentally impaired before transplantation realized no change in neurocognitive function 1 year later. These results suggest that liver transplantation may be an effective treatment for classic MSUD; while it may arrest brain damage, it will not reverse it.[8] 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.[9]
  • 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.
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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.

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Activity

Do not restrict activity.

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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  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; Biomarin Consulting fee Review panel membership

Specialty Editor Board

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

Disclosure: Nothing to disclose.

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.

Leonard G Feld, MD, PhD, MMM, FAAP  Sara H Bissell and Howard C Bissell Endowed Chair in Pediatrics, Chief Medical Officer, Levine Children's Hospital, Carolinas Medical Center

Leonard G Feld, MD, PhD, MMM, FAAP 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.

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 and Genetics, Director RSA, 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.

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. Park HD, Lee DH, Hong YH, Kang DH, Lee YK, Song J, et al. Three Korean patients with maple syrup urine disease: four novel mutations in the BCKDHA gene. Ann Clin Lab Sci. Spring 2011;41(2):167-73. [Medline].

  7. 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].

  8. Mazariegos GV, Morton DH, Sindhi R, et al. Liver transplantation for classical maple syrup urine disease: long-term follow-up in 37 patients and comparative United network for organ sharing experience. J Pediatr. Jan 2012;160(1):116-121.e1. [Medline].

  9. Mazariegos GV, Morton DH, Sindhi R, Soltys K, Nayyar N, Bond G, et al. Liver Transplantation for Classical Maple Syrup Urine Disease: Long-Term Follow-Up in 37 Patients and Comparative United Network for Organ Sharing Experience. J Pediatr. Aug 10 2011;[Medline].

  10. 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.

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

  12. 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].

  13. 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].

  14. 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].

  15. 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].

  16. 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].

  17. 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].

  18. 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].

  19. 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].

  20. 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].

  21. 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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