Skip Navigation
Genetics Home Reference: your guide to understanding genetic conditions
http://ghr.nlm.nih.gov/     A service of the U.S. National Library of Medicine®

Maple syrup urine disease

Reviewed December 2013

What is maple syrup urine disease?

Maple syrup urine disease is an inherited disorder in which the body is unable to process certain protein building blocks (amino acids) properly. The condition gets its name from the distinctive sweet odor of affected infants' urine. Beginning in early infancy, this condition is characterized by poor feeding, vomiting, lack of energy (lethargy), and developmental delay. If untreated, maple syrup urine disease can lead to seizures, coma, and death.

Maple syrup urine disease is often classified by its pattern of signs and symptoms. The most common and severe form of the disease is the classic type, which becomes apparent soon after birth. Variant forms of the disorder become apparent later in infancy or childhood and are typically milder, but they still involve developmental delay and other medical problems if not treated.

How common is maple syrup urine disease?

Maple syrup urine disease affects an estimated 1 in 185,000 infants worldwide. The disorder occurs much more frequently in the Old Order Mennonite population, with an estimated incidence of about 1 in 380 newborns.

What genes are related to maple syrup urine disease?

Mutations in the BCKDHA, BCKDHB, DBT, and DLD genes can cause maple syrup urine disease. These four genes provide instructions for making proteins that work together as a complex. The protein complex is essential for breaking down the amino acids leucine, isoleucine, and valine, which are present in many kinds of food (particularly protein-rich foods such as milk, meat, and eggs).

Mutations in any of these four genes reduce or eliminate the function of the protein complex, preventing the normal breakdown of leucine, isoleucine, and valine. As a result, these amino acids and their byproducts build up in the body. Because high levels of these substances are toxic to the brain and other organs, their accumulation leads to the serious medical problems associated with maple syrup urine disease.

Related Gene(s)

Changes in these genes are associated with maple syrup urine disease.

  • BCKDHA
  • BCKDHB
  • DBT
  • DLD

How do people inherit maple syrup urine disease?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of maple syrup urine disease?

These resources address the diagnosis or management of maple syrup urine disease and may include treatment providers.

  • Baby's First Test (http://www.babysfirsttest.org/newborn-screening/conditions/maple-syrup-urine-disease-msud)
  • Gene Review: Maple Syrup Urine Disease (http://www.ncbi.nlm.nih.gov/books/NBK1319/)
  • Gene Review: Organic Acidemias (http://www.ncbi.nlm.nih.gov/books/NBK1134/)
  • Genetic Testing Registry: Maple syrup urine disease (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0024776)
  • MedlinePlus Encyclopedia: Maple Syrup Urine Disease (http://www.nlm.nih.gov/medlineplus/ency/article/000373.htm)

You might also find information on the diagnosis or management of maple syrup urine disease in Educational resources (http://www.ghr.nlm.nih.gov/condition/maple-syrup-urine-disease/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/maple-syrup-urine-disease/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about maple syrup urine disease?

You may find the following resources about maple syrup urine disease helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for maple syrup urine disease?

  • BCKD deficiency
  • branched-chain alpha-keto acid dehydrogenase deficiency
  • branched-chain ketoaciduria
  • ketoacidemia
  • MSUD

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about maple syrup urine disease?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding maple syrup urine disease?

acids ; amino acid ; autosomal ; autosomal recessive ; breakdown ; cell ; coma ; deficiency ; dehydrogenase ; developmental delay ; gene ; incidence ; inherited ; isoleucine ; lethargy ; leucine ; metabolism ; newborn screening ; population ; protein ; recessive ; screening ; thiamine ; toxic ; valine

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Carleton SM, Peck DS, Grasela J, Dietiker KL, Phillips CL. DNA carrier testing and newborn screening for maple syrup urine disease in Old Order Mennonite communities. Genet Test Mol Biomarkers. 2010 Apr;14(2):205-8. doi: 10.1089/gtmb.2009.0107. (http://www.ncbi.nlm.nih.gov/pubmed/20136525?dopt=Abstract)
  • Chuang DT, Chuang JL, Wynn RM. Lessons from genetic disorders of branched-chain amino acid metabolism. J Nutr. 2006 Jan;136(1 Suppl):243S-9S. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16365091?dopt=Abstract)
  • Gene Review: Maple Syrup Urine Disease (http://www.ncbi.nlm.nih.gov/books/NBK1319/)
  • 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. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15930470?dopt=Abstract)
  • Morton DH, Strauss KA, Robinson DL, Puffenberger EG, Kelley RI. Diagnosis and treatment of maple syrup disease: a study of 36 patients. Pediatrics. 2002 Jun;109(6):999-1008. (http://www.ncbi.nlm.nih.gov/pubmed/12042535?dopt=Abstract)
  • Puffenberger EG. Genetic heritage of the Old Order Mennonites of southeastern Pennsylvania. Am J Med Genet C Semin Med Genet. 2003 Aug 15;121C(1):18-31. (http://www.ncbi.nlm.nih.gov/pubmed/12888983?dopt=Abstract)
  • Simon E, Flaschker N, Schadewaldt P, Langenbeck U, Wendel U. Variant maple syrup urine disease (MSUD)--the entire spectrum. J Inherit Metab Dis. 2006 Dec;29(6):716-24. Epub 2006 Oct 25. (http://www.ncbi.nlm.nih.gov/pubmed/17063375?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: December 2013
Published: August 18, 2014