Spectrum analysis of inborn errors of metabolism for expanded newborn screening in Xinjiang, China

Jingying Zhu; Li Han; Pingjingwen Yang; Ziyi Feng; Shuyuan Xue

doi:10.7717/peerj.18173

Spectrum analysis of inborn errors of metabolism for expanded newborn screening in Xinjiang, China

PeerJ. 2024 Dec 9:12:e18173. doi: 10.7717/peerj.18173. eCollection 2024.

Authors

Jingying Zhu^#^{1

2}, Li Han³, Pingjingwen Yang¹, Ziyi Feng¹, Shuyuan Xue^#^{1

2}

Affiliations

¹ Prenatal Diagnosis Center, Urumqi Maternal and Child Health Hospital, Urumqi, Xinjiang Uygur Autonomous Region, China.
² Xinjiang Clinical Research Center for Perinatal Diseases, Urumqi, China.
³ Neonatal Department, Urumqi Maternal and Child Health Hospital, Urumqi, Xinjiang Uygur Autonomous Region, China.

^# Contributed equally.

Abstract

To determine the disease spectrum and genetic characteristics of inborn errors of metabolism (IEM) in Xinjiang province in the northwest of China, 41,690 newborn babies were screening by tandem mass spectrometry from November 2018 to December 2021. Of these, 57 newborn babies were referred for genetic analysis by next-generation sequencing, which was validated by Sanger sequencing. A total of 36 newborn babies and one relative were diagnosed with IEM, and the overall positive predictive value was 29.03%. The overall incidence of IEM in Xinjiang was 1:1,158 (36/41,690). The incidence of amino acidemias, organic acidemias, and fatty acid oxidation disorder were 1:1,668 (25/41,690), 1:4,632 (9/41,690), and 1:20,845 (2/41,690), respectively. Phenylketonuria and methylmalonic acidemia were the two most common inborn errors of metabolism (IEM), accounting for 83% (30/36) of all confirmed cases. Some hotspot mutations were observed for several IEMs, including PAH gene c.158G > A (p.Arg53His) and c.688G > A (p.Val230Ile) for hyperphenylalaninemia. Four mutation types of the MMACHC gene (e.g., c.609G > A (p.Trp203Ter), c.567dupT (p.Ile190fs)) and six mutation types of the MMUT gene (e.g., c.729_730insT (p.Asp244fs)) were found for methylmalonic acidemia. We also found 11 mutations in six genes: PCCB, IVD, GCDH, MCCC1, SLC22A5, and ACADS in this region. This study combined tandem mass spectrometry and next-generation sequencing technology for the screening and diagnosis of IEM. The study provides effective clinical guidance, and the data provide a basis for expanding newborn screening, genetic screening, and IEM gene consultation in Xinjiang, China.

Keywords: Genetic characteristics; Inborn errors of metabolism; Next generation sequencing; Tandem mass spectrometry.

MeSH terms

Amino Acid Metabolism, Inborn Errors / diagnosis
Amino Acid Metabolism, Inborn Errors / epidemiology
Amino Acid Metabolism, Inborn Errors / genetics
China / epidemiology
Female
Genetic Testing / methods
High-Throughput Nucleotide Sequencing
Humans
Incidence
Infant, Newborn
Male
Metabolism, Inborn Errors* / diagnosis
Metabolism, Inborn Errors* / epidemiology
Metabolism, Inborn Errors* / genetics
Mutation
Neonatal Screening* / methods
Phenylketonurias* / diagnosis
Phenylketonurias* / epidemiology
Phenylketonurias* / genetics
Tandem Mass Spectrometry*

Supplementary concepts

Methylmalonic acidemia

Grants and funding

This work was supported by the Natural Science Foundation of Xinjiang Uygur Autonomous Region, China (No. 2021D01B16) and the Science and Technology Innovation Team (Tianshan Innovation Team) Program (No. 2022TSYCTD0016). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.