OMIA:000627-9913 : Maple syrup urine disease, BCKDHA-realted in Bos taurus (taurine cattle)

Categories: Homeostasis / metabolism phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 248600 (trait) , 608348 (gene)

Links to relevant human diseases in MONDO:

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 1990

Species-specific description: Maple Syrup Urine Disease (MSUD) is an autosomal recessive defect reported in Poll Hereford (PH) and Poll Shorthorn (PS) calves (Harper et al., 1986; Healy et al., 1992). The clinical, biochemical and pathological characters of the disease are identical in the two breeds of cattle, and are characterised by the rapid onset of progressive neurological disease, resulting in death within a few days of birth. The disease is caused by a deficiency of activity of the mitochondrial enzyme branched-chain alpha-keto acid dehydrogenase (BCKADH). This deficiency leads to elevated concentrations of branched chain alpha-keto acids and their precursors, the branched chain amino acids, valine, leucine and isoleucinein in blood and tissues. BCKADH consists of four subunits E1alpha, E1beta, E2 and E3 that are encoded by separate genes, and MSUD may result from deficiency of any of the subunits (Mohammad Shariflou 3/11/2006).

Molecular basis: By cloning and sequencing a very likely comparative candidate gene (based on the homologous human disorder), Zhang et al. (1990) reported a nonsense mutation (248C>T) in the leader region of the gene for the E1 alpha subunit (BCKDHA) as the cause of the disorder in Poll Herefords. A 1380C>T transition in the same gene was reported by Dennis and Healy (1999) to be responsible for the disease in Poll Shorthorns (Mohammad Shariflou 3/11/2006; FN 14/9/2011).

Genetic testing: A PCR test to genotype this disease in Poll Shorthorns and Poll Herefords was developed by Dennis and Healy (1999).

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
BCKDHA branched chain keto acid dehydrogenase E1, alpha polypeptide Bos taurus 18 NC_037345.1 (50541524..50560679) BCKDHA Homologene, Ensembl , NCBI gene


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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.

OMIA Variant ID Breed(s) Variant Phenotype Gene Allele Type of Variant Source of Genetic Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
298 Polled Hereford (Cattle) Maple syrup urine disease BCKDHA nonsense (stop-gain) Naturally occurring variant ARS-UCD1.2 18 g.50551011C>T c.148C>T p.(Q50*) cDNA position based on ENSBTAT00000021342.6 1990 2303405
200 Shorthorn (Cattle) Maple syrup urine disease BCKDHA missense Naturally occurring variant ARS-UCD1.2 18 g.50560242C>T c.1380C>T p.(P372L) 1999 10425233 Breed and variant information kindly provided or confirmed by Matt McClure and Jennifer McClure from "Understanding Genetics and Complete Genetic Disease and Trait Definition (Expanded 2016 Edition)" (

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2012). OMIA:000627-9913: Online Mendelian Inheritance in Animals (OMIA) [dataset].


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.

2021 Konovalova, E., Romanenkova, O., Kostyunina, O., Gladyr, E. :
The molecular bases study of the inherited diseases for the health maintenance of the beef cattle. Genes (Basel) 12:678, 2021. Pubmed reference: 33946496. DOI: 10.3390/genes12050678.
2020 Konovalova, EN., Romanenkova, OS., Volkova, VV., Kostyunina, OV. :
DNA analysis of the Russian populations of Aberdeen Angus, Hereford and Belgian Blue cattle Arch Anim Breed 63:409-416, 2020. DOI: 10.5194/aab-63-409-2020.
2019 Zepeda-Batista, J.L., Parra-Bracamonte, G.M., Núñez-Domínguez, R., Ramírez-Valverde, R., Ruíz-Flores, A., Zepeda-Batista, J.L., Parra-Bracamonte, G.M., Núñez-Domínguez, R., Ramírez-Valverde, R., Ruíz-Flores, A. :
Screening genetic diseases prevalence in Braunvieh cattle. Trop Anim Health Prod 51:25-31, 2019. Pubmed reference: 30014197. DOI: 10.1007/s11250-018-1655-y.
2011 Windsor, P., Kessell, A., Finnie, J. :
Neurological diseases of ruminant livestock in Australia. V: congenital neurogenetic disorders of cattle. Aust Vet J 89:394-401, 2011. Pubmed reference: 21933167. DOI: 10.1111/j.1751-0813.2011.00826.x.
2009 Skvorak, K.J. :
Animal models of maple syrup urine disease. J Inherit Metab Dis 32:229-46, 2009. Pubmed reference: 19263237. DOI: 10.1007/s10545-009-1086-z.
2005 Kato, K., Uchida, K., Murakami, T., Tateyama, S. :
A neurological disease with spongy degeneration in a newborn Japanese black calf. J Vet Med Sci 67:1067-70, 2005. Pubmed reference: 16276067.
O'Toole, D., Montgomery, DL., Steadman, L., O'Rourke, B., Russell, W., Dennis, J. :
Status spongiosus of white matter in newborn Gelbvieh-cross calves. J Vet Diagn Invest 17:546-53, 2005. Pubmed reference: 16475512.
2002 Healy, P.J., Dennis, J.A., Windsor, P.A., Pierce, K.D., Schofield, P.R. :
Genotyping cattle for inherited congenital myoclonus and maple syrup urine disease Australian Veterinary Journal 80:695-697, 2002. Pubmed reference: 12465829.
1999 Dennis, J.A., Healy, P.J. :
Definition of the mutation responsible for maple syrup urine disease in Poll Shorthorns and genotyping Poll Shorthorns and Poll Herefords for maple syrup urine disease alleles Research in Veterinary Science 67:1-6, 1999. Pubmed reference: 10425233. DOI: 10.1053/rvsc.1998.0296.
1995 Healy, P.J., Dennis, J.A., Moule, J.F. :
Use of hair root as a source of DNA for the detection of heterozygotes for recessive defects in cattle Australian Veterinary Journal 72:392, 1995. Pubmed reference: 8599573.
Healy, P.J., Dennis, J.A. :
Heterozygote detection for maple syrup urine disease in cattle Australian Veterinary Journal 72:346-348, 1995. Pubmed reference: 8585849.
1994 Healy, P.J., Dennis, J.A. :
Molecular heterogeneity for bovine maple syrup urine disease Animal Genetics 25:329-332, 1994. Pubmed reference: 7818167.
Meng, M.H., Chuang, D.T. :
Site-directed mutagenesis and functional analysis of the active-site residues of the E2 component of bovine branched- chain alpha-keto acid dehydrogenase complex Biochemistry 33:12879-12885, 1994. Pubmed reference: 7947694.
1993 Healy, P.J., Dennis, J.A. :
Inherited Enzyme Deficiencies in Livestock Veterinary Clinics of North America - Food Animal Practice 9:55-63, 1993. Pubmed reference: 8457930.
1992 Dodd, P.R., Williams, S.H., Gundlach, A.L., Harper, P.A.W., Healy, P.J., Dennis, J.A., Johnston, G.A.R. :
Glutamate and gamma-Aminobutyric Acid Neurotransmitter Systems in the Acute Phase of Maple Syrup Urine Disease and Citrullinemia Encephalopathies in Newborn Calves Journal of Neurochemistry 59:582-590, 1992. Pubmed reference: 1352800.
1991 Chuang, D.T., Fisher, C.W., Lau, K.S., Griffin, T.A., Wynn, R.M., Cox, R.P. :
Maple Syrup Urine Disease - Domain Structure, Mutations and Exon Skipping in the Dihydrolipoyl Transacylase (E2) Component of the Branched-Chain alpha-Keto Acid Dehydrogenase Complex Molecular Biology & Medicine 8:49-63, 1991. Pubmed reference: 1943690.
Healy, P.J., Dennis, J.A., Harper, P.A.W., Graham, R., Reuter, R.E. :
Maple Syrup Urine Disease in Poll Shorthorn Calves Australian Veterinary Journal 69:143-144, 1991.
Lee, H.Y., Hall, T.B., Kee, S.M., Tung, H.Y.L., Reed, L.J. :
Purification and Properties of Branched-Chain alpha-Keto Acid Dehydrogenase Kinase from Bovine Kidney Biofactors 3:109-112, 1991. Pubmed reference: 1910451.
Mitsubuchi, H., Nobukuni, Y., Akaboshi, I., Indo, Y., Endo, F., Matsuda, I. :
Maple Syrup Urine Disease Caused by a Partial Deletion in the Inner E2 Core Domain of the Branched Chain alpha-Keto Acid Dehydrogenase Complex Due to Aberrant Splicing - A Single Base Deletion at a 5'-Splice Donor Site of an Intron of the E2 Gene Disrupts the Consensus Sequence in This Region Journal of Clinical Investigation 87:1207-1211, 1991. Pubmed reference: 2010537. DOI: 10.1172/JCI115120.
1990 Harper, P.A.W., Healy, P.J., Dennis, J.A. :
Animal Model of Human Disease - Maple Syrup Urine Disease (Branched Chain Ketoaciduria) American Journal of Pathology 136:1445-1447, 1990. Pubmed reference: 2356868.
Nobukuni, Y., Mitsubuchi, H., Endo, F., Asaka, J., Oyama, R., Titani, K., Matsuda, I. :
Isolation and Characterization of a Complementary DNA Clone Coding for the E1-Beta Subunit of the Bovine Branched-Chain Alpha-Ketoacid Dehydrogenase Complex - Complete Amino Acid Sequence of the Precursor Protein and Its Proteolytic Processing Biochemistry 29:1154-1160, 1990. Pubmed reference: 2322554.
Zhang, B., Healy, P.J., Zhao, Y., Crabb, D.W., Harris, R.A. :
Premature Translation Termination of the Pre-E1-Alpha-Subunit of the Branched Chain Alpha-Ketoacid Dehydrogenase As a Cause of Maple Syrup Urine Disease in Polled Hereford Calves Journal of Biological Chemistry 265:2425-2427, 1990. Pubmed reference: 2303405.
1989 Harper, P.A.W., Dennis, J.A., Healy, P.J., Brown, G.K. :
Maple syrup urine disease in calves: a clinical, pathological and biochemical study Australian Veterinary Journal 66:46-49, 1989. Pubmed reference: 2712767.
1988 Hu, C.W., Lau, K.S., Griffin, T.A., Chuang, J.L., Fisher, C.W., Cox, R.P., Chuang, D.T. :
Isolation and sequencing of a cDNA encoding the decarboxylase (E1)alpha precursor of bovine branched-chain alpha-keto acid dehydrogenase complex. Expression of E1alpha mRNA and subunit in maple-syrup-urine-disease and 3T3-L1 cells Journal of Biological Chemistry 263:9007-9014, 1988. Pubmed reference: 3379058.
1987 Baird, J.D., Wojcinski, Z.W., Wise, A.P., Godkin, M.A. :
Maple syrup urine disease in five Hereford calves in Ontario Canadian Veterinary Journal 28:505-511, 1987.
1986 Harper, P.A.W., Healy, P.J., Dennis, J.A. :
Ultrastructural findings in maple syrup urine disease in Poll hereford calves Acta Neuropathologica 71:316-320, 1986. Pubmed reference: 3799144.
Harper, P.A.W., Healy, P.J., Dennis, J.A. :
Maple syrup urine disease as a cause of spongiform encephalopathy in calves Veterinary Record 119:62-65, 1986. Pubmed reference: 3529596.

Edit History

  • Created by Mohammad Shariflou on 06 Nov 2006
  • Changed by Frank Nicholas on 14 Sep 2011
  • Changed by Frank Nicholas on 09 Dec 2011
  • Changed by Frank Nicholas on 23 Mar 2012
  • Changed by Frank Nicholas on 19 Sep 2012