Newborn Screening for Inborn Errors of Metabolism by Next-Generation Sequencing Combined with Tandem Mass Spectrometry

• Published in: International journal of neonatal screening Vol. 10; no. 2; p. 28
• Main Authors: Tang, Chengfang, Li, Lixin, Chen, Ting, Li, Yulin, Zhu, Bo, Zhang, Yinhong, Yin, Yifan, Liu, Xiulian, Huang, Cidan, Miao, Jingkun, Zhu, Baosheng, Wang, Xiaohua, Zou, Hui, Han, Lianshu, Feng, Jizhen, Huang, Yonglan
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 29.03.2024; MDPI
• Subjects: Amino acids; Childrens health; Disease; Fatty acids; Genes; Genomics; Health aspects; Hospitals; inborn errors of metabolism; Infants (Newborn); Mass spectrometry; Maternal & child health; Medical screening; Metabolism; Metabolism, Inborn errors of; Metabolites; newborn screening; next-generation sequencing; Oxidation; Scientific imaging; Statistical analysis; tandem mass spectrometry; Massachusetts; China; United States > US; inborn errors of metabolism; tandem mass spectrometry; next-generation sequencing; newborn screening
• ISSN: 2409-515X; 2409-515X
• DOI: 10.3390/ijns10020028

The aim of this study was to observe the outcomes of newborn screening (NBS) in a certain population by using next-generation sequencing (NGS) as a first-tier screening test combined with tandem mass spectrometry (MS/MS). We performed a multicenter study of 29,601 newborns from eight screening centers with NBS via NGS combined with MS/MS. A custom-designed panel targeting the coding region of the 142 genes of 128 inborn errors of metabolism (IEMs) was applied as a first-tier screening test, and expanded NBS using MS/MS was executed simultaneously. In total, 52 genes associated with the 38 IEMs screened by MS/MS were analyzed. The NBS performance of these two methods was analyzed and compared respectively. A total of 23 IEMs were diagnosed via NGS combined with MS/MS. The incidence of IEMs was approximately 1 in 1287. Within separate statistical analyses, the positive predictive value (PPV) for MS/MS was 5.29%, and the sensitivity was 91.3%. However, for genetic screening alone, the PPV for NGS was 70.83%, with 73.91% sensitivity. The three most common IEMs were methylmalonic academia (MMA), primary carnitine deficiency (PCD) and phenylketonuria (PKU). The five genes with the most common carrier frequencies were (1:42), (1:51), (1:52), (1:55) and (1:63). Our study showed that NBS combined with NGS and MS/MS improves the performance of screening methods, optimizes the process, and provides accurate diagnoses.