Menkes et al.1 first described MSUD in 1954, stating that the most common clinical signals presented by MSUD patients included ketoacidosis, hypoglycemia, opisthotonos, poor feeding, apnea, ataxia, convulsions, coma, psychomotor delay and mental retardation. The diagnosis is made by demonstrating raised plasma levels of valine, leucine and isoleucine by one-dimensional chromatography with the solvent system butanol-acetic acid water.1 The raised plasma levels of these amino acids indicate interference in their normal metabolic pathways. 2

Furthermore, this accumulation lays stress on the early and rapidly developing brain, which may be due to the competitive inhibition of glutamic acid decarboxylation, an important brain function, by the …show more content…
4 After Norton et al. 5 identified alloisoleucine as another major indicator in 1962, researchers began investigating its mechanism on how it is formed in the human body (Figure 2). L-alloisoleucine (2S, 3R), a diastereoisomer of L-isoleucine (2S, 3S), and the two keto-acids, (S) and (R) 2-keto-3-methylvaleric acid (KMVA), are normal constituents of the human plasma.6 It has been proposed that the catabolism of the diastereoisomers, L-isoleucine and L-alloisolecuine, is initiated by reversible transamination catalyzed by branched-chain L-amino acid aminotransferase. 7,8 The chiral center of KMVA has been proposed to racemize through non-enzymatic keto-enol tautomerism to yield R and S isomers proposed by Meister and White9 in 1951 (Figure 3). S- and R-KMVA, once formed, are oxidatively decarboxylated by the BCKAD, which leads to the formation of the S- and R-branched-chain-acyl-CoA derivatives. 10,11,12 In our body these pathways may function as a relief mechanism against unavoidable appearance of the keto-acids. 13 However, in MSUD the keto-acids can escape degradation and be transported into the extracellular space or be diverted and accumulated with L-alloisoleucine.