Fourteen new mutations of , and genes associated with maple syrup urine disease (MSUD) in Malaysian population.

Maple syrup urine disease (MSUD) is a rare autosomal recessive metabolic disorder. This disorder is usually caused by mutations in any one of the genes; , and , which represent E1α, E1β and E2 subunits of the branched-chain α-keto acid dehydrogenase (BCKDH) complex, respectively. This study presents the molecular characterization of 31 MSUD patients. Twenty one mutations including 14 new mutations were identified. The gene was the most commonly affected (45.2%) compared to gene (16.1%) and gene (38.7%). webservers predicted all mutations were disease-causing. In addition, structural evaluation disclosed that all new missenses in , and genes affected stability and formation of E1 and E2 subunits. Majority of the patients had neonatal onset MSUD (26 of 31). Meanwhile, the new mutation; c.1196C > G (p.S399C) in gene was noted to be recurrent and found in 9 patients. : Our findings have expanded the mutational spectrum of the MSUD and revealed the genetic heterogeneity among Malaysian MSUD patients. We also discovered the p.S399C from gene was noted as a recurrent mutation in Malay community and it suggested the existence of common and unique mutation in Malay population.