Phenotype Details
Phene ID
1202
Name
Maple syrup urine disease, BCKDHA-related
Phene Name
N/A
OMIA ID
627
Species ID
9913
Characterised
Yes
Characterised Year
1990
Linked Genes
SymbolGene IDChromosomeDescription
BCKDHA28214918branched chain keto acid dehydrogenase E1, alpha polypeptide
Linked Variants
Variant IDPhenotypeGene IDDeleteriousChromosomeGenomicTranscriptProtein
200Maple syrup urine disease282149118g.50560242C>Tc.1380C>Tp.(P372L)
298Maple syrup urine disease282149118g.50551011C>Tc.148C>Tp.(Q50*)
Linked Breeds
BreedBreed IDSpecies IDVBO Term
Polled Hereford (Cattle)959913http://purl.obolibrary.org/obo/VBO_0000341
Shorthorn (Cattle)769913http://purl.obolibrary.org/obo/VBO_0000375
Summary

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 Genetics

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 Test

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

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