OBJECTIVETo explore the genetic etiology of a patient with classic maple syrup urine disease (MSUD).

METHODSNext-generation sequencing (NGS) was used to screen the exons of BCKDHA, BCKDHB, DBT and DLD genes. Suspected mutations were verified by Sanger sequencing. Bioinformatic analysis was carried out to predict the influence of mutations on the protein structure and function.

RESULTSNGS and Sanger sequencing have detected a c.550delT mutation in exon 5 of the BCKDHB gene in the mother and a c.1046G>A mutation in exon 10 of the BCKDHB gene in the father, while no mutation was found with BCKDHA, DBT and DLD genes. Among these, the c.550delT is a novel mutation. Bioinformatic analysis suggested that the two mutations both located in a highly conserved region and may decrease the activity of branched-chain α-ketoacid dehydrogenase complex through alternation of its structure.

CONCLUSIONThe compound heterozygous mutations c.550delT and c.1046G>A of the BCKDHB gene probably underlie the clinical manifestations of the patient with classic MSUD.