Skip navigation

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites.

URL of this page:


branched chain keto acid dehydrogenase E1 subunit alpha

Normal Function

The BCKDHA gene provides instructions for making one part, the alpha subunit, of a group of enzymes called the branched-chain alpha-keto acid dehydrogenase (BCKD) enzyme complex. Two alpha subunits connect with two beta subunits, which are produced from the BCKDHB gene, to form a critical piece of the enzyme complex called the E1 component.

The BCKD enzyme complex is responsible for one step in the normal breakdown of three protein building blocks (amino acids). These amino acids—leucine, isoleucine, and valine—are obtained from the diet. They are present in many kinds of food, particularly protein-rich foods such as milk, meat, and eggs. The BCKD enzyme complex is active in mitochondria, which are specialized structures inside cells that serve as energy-producing centers. The breakdown of leucine, isoleucine, and valine produces molecules that can be used for energy.

Health Conditions Related to Genetic Changes

Maple syrup urine disease

More than 80 mutations in the BCKDHA gene have been identified in people with maple syrup urine disease. These mutations most often cause the severe, classic form of the disorder, which becomes apparent soon after birth. Maple syrup urine disease gets its name from the distinctive sweet odor of affected infants' urine. It is also characterized by poor feeding, vomiting, lack of energy (lethargy), abnormal movements, and delayed development.

Most BCKDHA mutations change single amino acids in the alpha subunit of the BCKD enzyme complex. In the Old Order Mennonite population, where maple syrup urine disease occurs frequently, the most common mutation replaces the amino acid tyrosine with the amino acid asparagine at position 438 (written as Tyr438Asn or Y438N).

Mutations in the BCKDHA gene disrupt the normal function of the BCKD enzyme complex, preventing it from effectively breaking down leucine, isoleucine, and valine. As a result, these amino acids and their byproducts build up in the body. This accumulation is toxic to cells and tissues, particularly in the nervous system. The buildup of these substances can lead to seizures, developmental delay, and the other health problems associated with maple syrup urine disease.

More About This Health Condition

Other Names for This Gene

  • BCKDH E1-alpha
  • branched chain keto acid dehydrogenase E1, alpha polypeptide (maple syrup urine disease)
  • MSUD1

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Gene and Variant Databases


  • Flaschker N, Feyen O, Fend S, Simon E, Schadewaldt P, Wendel U. Description of the mutations in 15 subjects with variant forms of maple syrup urine disease. J Inherit Metab Dis. 2007 Nov;30(6):903-9. doi: 10.1007/s10545-007-0579-x. Epub 2007 Oct 8. Citation on PubMed
  • Henneke M, Flaschker N, Helbling C, Muller M, Schadewaldt P, Gartner J, Wendel U. Identification of twelve novel mutations in patients with classic and variant forms of maple syrup urine disease. Hum Mutat. 2003 Nov;22(5):417. doi: 10.1002/humu.9187. Citation on PubMed
  • 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. doi: 10.1002/ajmg.c.20003. Citation on PubMed
  • Quental S, Macedo-Ribeiro S, Matos R, Vilarinho L, Martins E, Teles EL, Rodrigues E, Diogo L, Garcia P, Eusebio F, Gaspar A, Sequeira S, Furtado F, Lanca I, Amorim A, Prata MJ. 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. doi: 10.1016/j.ymgme.2008.02.008. Epub 2008 Apr 2. Citation on PubMed
  • Rodriguez-Pombo P, Navarrete R, Merinero B, Gomez-Puertas P, Ugarte M. Mutational spectrum of maple syrup urine disease in Spain. Hum Mutat. 2006 Jul;27(7):715. doi: 10.1002/humu.9428. Citation on PubMed
  • Strauss KA, Puffenberger EG, Carson VJ. Maple Syrup Urine Disease. 2006 Jan 30 [updated 2020 Apr 23]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from Citation on PubMed

The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.