Results of tandem mass spectrometry screening and gene mutation analysis of neonatal amino acid metabolic diseases in Jining, Shandong province
Liu Li , Yang Chiju , Chen Xigui， et al
(1. Department of Pathology, Jining First People's Hospital, Shandong, Jining 272000, China; 2. Neonatal Disease Screening Center, Jining Maternal and Child Health and Family Planning Service Center, Shandong, Jining 272000, China; 3. Clinical Laboratory, Jining Maternal and Child Health and Family Planning Service Center, Shandong, Jining 272000, China)
【Abstract】Objective To understand the prevalence rate, disease composition and gene variant type
of neonatal amino acid metabolic diseases in Jining, Shandong province. Method From July 2014 to
December 2021, the heel blood of newborns was collected to detect the blood amino acid concentration
by tandem mass spectrometry and screened for amino acid metabolic diseases in Jining Neonatal Disease
Screening Center of Shandong Province. Mutated genes were detected by nucleic acid mass spectrometry andsecond-generation sequencing and verified by Sanger sequencing. Non-normally distributed measurementdata were represented by median (range), count data were expressed by frequency and rate, and prevalencerate was expressed by 1/n. Result Of the 741 157 neonates, 883 cases of amino acid metabolic diseaseswere positive in MS/MS initial screening, and the positive rate was 0.12% (883/741 157), and 876 caseswith a positive recall of 99.21% (876/883). There were 145 cases of confirmed amino acid metabolicdiseases, a positive predictive value of 16.55% (145/876), a total prevalence of 1/5 111, 9 class diseases,phenylalanine hydroxylase defificiency was the most common, accounting for 56.55% (82/145), followed byhypermethioninemia and Hetering protein defificiency, accounting for 15.86% (23/145) and 10.34% (15/145),respectively. Compound heterozygous mutations in phenylalanine hydroxylase deficiency, Hitler proteindefificiency, tetrahydrobiopterin defificiency, citrullinemia type Ⅰ, arginine succinemia and tyrosinemia type Ⅲaccounting for 71.43%-100%; hypermethioninemia, maple iuria and ornithine carbamyltransferase defificiencywere mainly heterozygous mutations, accounting for 52.17%-100%. The PAH gene mutation site c.728G>A(p. R243Q), the MAT1A gene mutation site c.791G>A (p. R264H) and the SLC25A13 gene mutation sitec.852_855del (p. M285Pfs*2) had the highest detection rate. During the follow-up period, four cases withmaple iuria and one case with ornithine carbamidyltransferase defificiency died, and the remaining cases hadnormal growth and development. Conclusion The total prevalence rate of neonatal amino acid metabolicdiseases in Jining city of Shandong Province is 1/5 111. Phenylalanine hydroxylase defificiency is the mostcommon disease, and PAH gene mutation is predominant. c.728G>A (p.R243Q) is the hotspot mutation site.
[J]. 发育医学电子杂志, 2022, 10(6): 409-416.
Liu Li , Yang Chiju , Chen Xigui, et al. Results of tandem mass spectrometry screening and gene mutation analysis of neonatal amino acid metabolic diseases in Jining, Shandong province. Journal of Developmental Medicine(Electronic Version), 2022, 10(6): 409-416.
2022, Vol. 10 
