Deficiency of the E1β subunit in the branched-chain α-keto acid dehydrogenase complex due to a single base substitution to the intron 5, resulting in two alternatively spliced mRNAs in patient with maple syrup urine disease

1994 ◽  
Vol 1225 (3) ◽  
pp. 317-325 ◽  
Author(s):  
Y HAYASHIDA ◽  
H MITSUBUCHI ◽  
Y INDO ◽  
K OHTA ◽  
F ENDO ◽  
...  
Keyword(s):  
Maple Syrup Urine Disease ◽  
Base Substitution ◽  
Keto Acid ◽  
Maple Syrup ◽  
Single Base ◽  
Alternatively Spliced ◽  
Urine Disease ◽  
Branched Chain ◽  
Acid Dehydrogenase Complex ◽  
Dehydrogenase Complex

scholarly journals Branched Chain Amino Acids Induce Apoptosis in Neural Cells without Mitochondrial Membrane Depolarization or Cytochromec Release: Implications for Neurological Impairment Associated with Maple Syrup Urine Disease

2000 ◽  
Vol 11 (5) ◽  
pp. 1919-1932 ◽  
Author(s):  
Philippe Jouvet ◽  
Pierre Rustin ◽  
Deanna L. Taylor ◽  
Jennifer M. Pocock ◽  
Ursula Felderhoff-Mueser ◽  
...  
Keyword(s):  
Amino Acids ◽  
Cytochrome C ◽  
Maple Syrup Urine Disease ◽  
Mitochondrial Membrane ◽  
Branched Chain Amino Acids ◽  
Keto Acid ◽  
Maple Syrup ◽  
Mitochondrial Membrane Depolarization ◽  
Urine Disease ◽  
Branched Chain

Maple syrup urine disease (MSUD) is an inborn error of metabolism caused by a deficiency in branched chain α-keto acid dehydrogenase that can result in neurodegenerative sequelae in human infants. In the present study, increased concentrations of MSUD metabolites, in particular α-keto isocaproic acid, specifically induced apoptosis in glial and neuronal cells in culture. Apoptosis was associated with a reduction in cell respiration but without impairment of respiratory chain function, without early changes in mitochondrial membrane potential and without cytochrome c release into the cytosol. Significantly, α-keto isocaproic acid also triggered neuronal apoptosis in vivo after intracerebral injection into the developing rat brain. These findings suggest that MSUD neurodegeneration may result, at least in part, from an accumulation of branched chain amino acids and their α-keto acid derivatives that trigger apoptosis through a cytochrome c-independent pathway.

scholarly journals Maple Syrup Urine Disease in a Central Indiana Hereford Herd

2015 ◽  
Vol 2015 ◽  
pp. 1-4 ◽  
Author(s):  
Mark E. Robarge ◽  
Jonathan E. Beever ◽  
Stephen D. Lenz ◽  
Christopher J. Lynch ◽  
William L. Wigle
Keyword(s):  
Maple Syrup Urine Disease ◽  
Index Case ◽  
Clinical Signs ◽  
Maple Syrup ◽  
Hereford Cattle ◽  
Urine Disease ◽  
Branched Chain ◽  
Ketoacid Dehydrogenase ◽  
Dehydrogenase Complex ◽  
T Haplotype

Maple syrup urine disease (MSUD) and further cases were identified in herd mates of a small Hereford herd in Indiana based on history, clinical signs, microscopic lesions, and biochemical and genetic testing. This aminoacidopathy has been diagnosed in polled Shorthorn, polled Hereford, and Hereford cattle in Australia, Uruguay, Argentina, and Canada and is the result of a mutation of the branched-chain alpha-ketoacid dehydrogenase complex. The Indiana index calf case was confirmed by showing the classic accumulation of ketoacids in liver that results from a defect in the E1-alpha subunit (248 C/T haplotype) in the mitochondrial branched-chainα-ketoacid dehydrogenase complex. The presence of the mutation was confirmed in the index case, the dam, and four related herd mates that represent the first confirmed cases of bovine MSUD mutation in United States cattle.

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