A novel mutation in the DBT gene causes in an Azerbaijanian child classic maple syrup urine disease

Abstract

Maple syrup urine disease (MSUD) is a complicated disease that is inherited one. The maple syrup urine disease is accompanied with full or partial disorder of enzyme activity, participating in the metabolism of three amino acids as valine, leucine and isoleucine. If the process of valine, leucine and isoleucine metabolism is interrupted, then stockpiling and decay happens in the body. Decay products of those amino acids are evacuated from the body and are toxic. These toxins relate to biogenic amines – ptomaine. The presence of maple syrup metabolic disorder by biochemical and molecular genetic methods in Azerbaijan population confirms the importance of screening test of newborns for the respective disease. Homozygous substitution of adenine by guanine mutation has been found in DBT (dihydrolipoamide branched-chain transacylase) gene at 1199 nucleotide position (p. N400S 1199 A (Adenine) G (Guanine)). No mutations were identified in BCKDHA (branched-chain keto acid dehydrogenase E1, alpha polypeptide) and 2 Huseynova Lala Samaddin and Hagverdiyeva Raya Rustam BCKDHB (branched-chain keto acid dehydrogenase E1, beta polypeptide) genes. The identified mutation (1199 A (Adenine)-G (Guanine)) is a new mutation and has not been included in any literature. This mutation disrupts the metabolism of Valine, Leucine and Isoleucine amino acids and leads to maple syrup disease. For the diagnosis of maple syrup metabolic disorder the amount of valine, leucine and isoleucine amino acids was evaluated in the urine and plasma and the comparison of obtained results revealed that plasma analysis was more informative.