Tandem mass spectrometry screening and genetic analysis of neonates with Urea cycle disorders in Xuzhou region
10.3760/cma.j.cn511374-20240708-00379
- VernacularTitle:徐州地区尿素循环障碍类疾病的新生儿串联质谱筛查及基因变异分析
- Author:
Wei ZHOU
1
;
Huizhong LI
1
;
Li YANG
1
;
Fang SHAO
1
;
Maosheng GU
1
Author Information
1. 徐州市妇幼保健院医学遗传与产前诊断科，徐州 221009
- Publication Type:Journal Article
- Keywords:
Urea cycle disorders, inborn;
Gene variant;
Tandem mass spectrometry;
Newborn screening;
Ornithine carbamoyltransferase deficiency disease;
Carbamoyl-phosp
- From:
Chinese Journal of Medical Genetics
2025;42(1):26-33
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the results of four types of Urea cycle disorders (UCDs) in newborns from the Xuzhou region, assess the efficacy of newborn screening by tandem mass spectrometry (MS/MS), and analyze their genetic characteristics.Methods:A retrospective analysis was performed using tandem mass spectrometry to screen for inherited metabolic disorders in 691 712 newborns at the Maternal and Child Health Care Hospital of Xuzhou from November 2015 to December 2023. Ten children (cases 1-10) were diagnosed with Ornithine transcarbamylase deficiency (OTCD), Carbamoylphosphate synthase 1 deficiency (CPS1D), Arginase deficiency (ARGD), and Argininosuccinate synthase deficiency (ASSD) based on MS/MS and genetic testing. This study was approved by the Medical Ethics Committee of Xuzhou Maternity and Child Health Care Hospital (Ethics No.XZFY2024-051K-01J).Results:A total of 691 712 neonates were screened for UCDs using MS/MS, which identified 1 237, 1 237, 510, and 1 009 initial positive cases for OTCD, CPS1D, ASSD, and ARGD, respectively. After genetic testing, 1 case of OTCD, 1 case of CPS1D, 1 case of ASSD, and 7 cases of ARGD were confirmed. The overall positive predictive value for these four UCDs was 0.362%. Among the 10 diagnosed UCD cases, four novel variants were identified, which included OTC: c. 1024C>A (p.L342M) and ASS1: c. 826A>G (p.M276V), c.695C>T (p.P232L) and c. 694C>T (p.P232S). Bioinformatic analysis has rated these as variants of uncertain clinical significance or likely pathogenic based on guidelines from the American College of Medical Genetics and Genomics (ACMG). Conclusion:The incidence of four UCDs in neonates from the Xuzhou area is relatively low, and there is a correlation between genetic variants and clinical phenotypes. For novel variants with uncertain clinical significance or suspected pathogenicity, their pathogenicity should be clarified in conjunction with clinical and biochemical indicators. The four novel pathogenic variants of UCDs identified in this study have enriched the mutational spectrum of UCDs-associated genes in the Xuzhou region.
