Decreased BCKD activity is the main cause of increased BCAA levels and BCKAs in maple syrup urine disease, and plays a role in increased BCAA levels in diabetes type 2 and obesity.
BCAAs in plasma were normal in the two domino graft recipients, and the MSUD patient showed mildly elevated but stable BCAA concentrations despite an unrestricted diet.
Maple syrup urine disease (MSUD) is an autosomal recessive aminoacidopathy secondary to an enzyme defect in the catabolic pathway of the branched-chain amino acids (BCAAs: leucine, isoleucine, and valine).
Same BCKDK-knockdown in a MSUD patient fibroblasts unmasks the direct involvement of the accelerated BCAAs catabolism in the mitochondrial dysfunction.
A metabolic block in the oxidative decarboxylation of BCAA caused by mutations in the mitochondrial branched-chain alpha-keto acid dehydrogenase complex (BCKDC) results in Maple Syrup Urine Disease (MSUD) or branched-chain ketoaciduria.