Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Maple Syrup Urine Disease Treatment & Management

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

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.[15, 7, 14]

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.

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.

Next

Surgical Care

Three successful liver transplantations in patients with classic MSUD have been reported.[16] 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.[17] 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.[17]

Orthotopic liver transplantation performed at an experienced center has changed the outlook for patients with classic MSUD, who are frequently challenged with frequent episodes of metabolic decompensation. While liver transplantation is not able to reverse neurological damage that has already occurred, it can prevent additional episodes of decompensation and preserve neurological function. If performed early in the disease course, liver transplantation may guarantee normal or near-normal neurological outcomes.[17]

Previous
Next

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.

Previous
Next

Activity

Do not restrict activity.

Previous
 
 
Contributor Information and Disclosures
Author

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.

Coauthor(s)

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.

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

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

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

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

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

  6. Chuang DT, Shih VE. Maple syrup urine disease. 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.

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

  8. 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. 2011 Spring. 41(2):167-73. [Medline].

  9. 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. 2003 Nov. 22(5):417. [Medline].

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

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

  12. Quental S, Macedo-Ribeiro S, Matos R, Vilarinho L, Martins E, Teles EL, et al. Molecular and structural analyses of maple syrup urine disease and identification of a founder mutation in a Portuguese Gypsy community. Mol Genet Metab. 2008 Jun. 94(2):148-56. [Medline].

  13. 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. 2004 Feb. 163(2):76-80. [Medline].

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

  15. 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].

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

  17. 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. 2012. 160:116-121. [Medline].

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

  19. 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. 2006 Jan. 59(1):17-20. [Medline].

  20. 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. 2005 Jun. 135(6 Suppl):1565S-70S. [Medline].

  21. 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. 2003 Apr. 13(2):162-5. [Medline].

 
Previous
Next
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.