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

Chengfang Tang; Lixin Li; Ting Chen; Yulin Li; Bo Zhu; Yinhong Zhang; Yifan Yin; Xiulian Liu; Cidan Huang; Jingkun Miao; Baosheng Zhu; Xiaohua Wang; Hui Zou; Lianshu Han; Jizhen Feng; Yonglan Huang

doi:10.3390/ijns10020028

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

Int J Neonatal Screen. 2024 Mar 29;10(2):28. doi: 10.3390/ijns10020028.

Authors

Chengfang Tang¹, Lixin Li², Ting Chen³, Yulin Li⁴, Bo Zhu⁵, Yinhong Zhang⁶, Yifan Yin⁷, Xiulian Liu⁸, Cidan Huang⁸, Jingkun Miao⁷, Baosheng Zhu⁶, Xiaohua Wang⁵, Hui Zou⁴, Lianshu Han³, Jizhen Feng², Yonglan Huang¹

Affiliations

¹ Department of Guangzhou Newborn Screening Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou 510180, China.
² Department of Genetic, Shijiazhuang Maternal and Child Health Hospital, Shijiazhuang 050090, China.
³ Department of Pediatric Endocrinology and Genetic Metabolism, Shanghai Institute for Pediatric Research, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.
⁴ Neonatal Disease Screening Center, Jinan Maternity and Child Health Hospital Affiliated to Shandong First Medical University, Jinan 250001, China.
⁵ Department of Genetics, Inner Mongolia Maternity and Child Health Care Hospital, Hohhot 750306, China.
⁶ Department of Medical Genetics, NHC Key Laboratory of Preconception Health Birth in Western China, Yunnan Provincial Key Laboratory for Birth Defects and Genetic Diseases, Yunnan Provincial Clinical Research Center for Birth Defects and Rare Diseases, The First People's Hospital of Yunnan Province/The Affiliated Hospital of Kunming University of Science and Technology, Kunming 650032, China.
⁷ Department of Pediatrics, Chongqing Health Center for Women and Children &Women and Children's Hospital of Chongqing Medical University, Chongqing 401147, China.
⁸ Neonatal Disease Screening Center, Hainan Women and Children's Medical Center, Haikou 570206, China.

Abstract

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 PAH (1:42), PRODH (1:51), MMACHC (1:52), SLC25A13 (1:55) and SLC22A5 (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.

Keywords: inborn errors of metabolism; newborn screening; next-generation sequencing; tandem mass spectrometry.

Abstract

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