Abstract:

Objective: To determine the prevalence of citrin protein deficiency in neonates in Shijiazhuang, and further analyze the mutations of pathogenic genes. Methods: A total of 160 061 newborns in Shijiazhuang from January 2014 to December 2019 were detected for blood amino acid levels by tandem mass spectrometry (MS/MS), and the genetic testing were performed for suspected infants. Results: Among the 160 061 newborns, 20 cases were screened as positive cases, including 1 case confirmed the diagnosis with SLC25A13 gene testing; and 1 case that was false negative in newborn screening. The latter child patient was admitted to the hospital due to yellowish skin aggravated in less than 1 month. The blood tandem mass spectrometry showed that citrulline and methionine were elevated. The results of urine organic acids showed that 4-hydroxyphenyllactic acid and 4-hydroxyphenylpyruvic acid were both significantly increased. The prevalence of citrin protein deficiency in Shijiazhuang is 2/160 061. The gene testing showed that one case was a compound heterozygous mutation of SLC25A13 gene. The mutation sites were c.1021+1G>A and c.851_854delTATG. There was no report of c.1021+1G>A in the human gene mutation database. Conclusions: The application of tandem mass spectrometry in neonatal disease screening can detect the citrin protein deficiency as early as possible. Some newborn patients may be false negative screening; the gene testing is helpful for the diagnosis of citrin protein deficiency. The prevalence of citrin deficiency in Shijiazhuang area is 2/160 061. In this paper, we reported a novel mutation site of SLC25A13 gene.

Key words: Neonatal screening, Urea cycle disorders,inborn, Tandem mass spectrometry, Mutation, Citrin deficiency