Abstract:

Objective： To explore the prevalence rate of maple syrup urine disease (MSUD) in newborns, and to analyze the mutation characteristics of related genes in Shijiazhuang area, China. Methods： A total of 185 683 newborns born from January 2014 to December 2021 in Shijiazhuang area were screened for MSUD by tandem mass spectrometry, and BCKDHA, BCKDHB and DBT mutations were detected in newborns with positive screening. Results： Two children with MSUD were confirmed, with a prevalence rate of 1∶92 842. In two confirmed cases, the levels of blood leucine (Leu) and valine (Val) were elevated during initial screening. The levels of case 2 were also elevated in the review of tandem mass spectrometry, while case 1 died prematurely before being recalled for review and was not performed the review of tandem mass spectrometry. Two children with MSUD were all classic with gene complex heterozygous mutations of BCKDHB and DBT, and four mutations were found including c.331C>T, c.289G>T, c.75_76delAT and c.1359_1360delAG. Two unreported gene mutations were found, c.289G>T and c.1359_1360delAG. No mutations in the BCKDHA gene were detected. Case 1 died prematurely 10 days after birth. Case 2 began to develop symptoms 8 days after birth, and improved after timely intervention and treatment. Conclusions： Tandem mass spectrometry technology can be applied in newborn disease screening to detect early newborns with MSUD. The genetic testing can identify genetic causes and provide a basis for genetic counseling. The prevalence rate of MSUD in Shijiazhuang area was 1∶92 842. Four gene mutations, two of which were unreported gene mutations, were found in this study, enriching the gene mutation spectrum of MSUD.

Key words: Maple syrup urine disease, Amino acid metabolism, inborn errors, Neonatal screening, Tandem mass spectrometry, DNA mutational analysis