背景:如果不及时诊断或治疗,先天性代谢错误(IEM)通常会导致进行性和不可逆转的临床后果。基于串联质谱(MS/MS)的新生儿筛查(NBS)有助于IEM的早期诊断和治疗。本研究的目的是确定IEM的特征以及在19年时间内MS/MS筛查在上海的成功部署和应用。中国,通知国家国家统计局政策。
方法:通过MS/MS评估了1,176,073例新生儿干燥血斑中的氨基酸和酰基肉碱。IEM的诊断是通过综合考虑临床特征,生化性能和基因检测结果。在各种IEM亚型和基因型之间比较MS/MS测试参数的水平。
结果:从2003年1月到2022年6月,共有392名新生儿被诊断为IEM。有196例新生儿氨基酸紊乱(50.00%,1:5910),115例有机酸紊乱的新生儿(29.59%,1:10,139),和81例新生儿脂肪酸氧化紊乱(20.41%;1:14,701)。苯丙氨酸羟化酶缺乏症,甲基丙二酸血症和原发性肉碱缺乏症是三种最常见的疾病。八个IEM基因中的一些热点变异(PAH,SLC22A5,MMACHC,MMUT,MAT1A,MCCC2,ACADM,ACAD8),鉴定了35种新变体和一些基因型-生化表型关联。
结论:总共确定了28种IEM,上海的总体发病率为1:3000,中国。我们的研究为该市实施基于MS/MS的NBS和IEM的遗传咨询提供了临床指导。
BACKGROUND: Inborn errors of metabolism (IEMs) frequently result in progressive and irreversible clinical consequences if not be diagnosed or treated timely. The tandem mass spectrometry (MS/MS)-based newborn screening (NBS) facilitates early diagnosis and treatment of IEMs. The aim of this study was to determine the characteristics of IEMs and the successful deployment and application of MS/MS screening over a 19-year time period in Shanghai,
China, to inform national NBS policy.
METHODS: The amino acids and acylcarnitines in dried blood spots from 1,176,073 newborns were assessed for IEMs by MS/MS. The diagnosis of IEMs was made through a comprehensive consideration of clinical features, biochemical performance and genetic testing results. The levels of MS/MS testing parameters were compared between various IEM subtypes and genotypes.
RESULTS: A total of 392 newborns were diagnosed with IEMs from January 2003 to June 2022. There were 196 newborns with amino acid disorders (50.00%, 1: 5910), 115 newborns with organic acid disorders (29.59%, 1: 10,139), and 81 newborns with fatty acid oxidation disorders (20.41%; 1:14,701). Phenylalanine hydroxylase deficiency, methylmalonic acidemia and primary carnitine deficiency were the three most common disorders. Some hotspot variations in eight IEM genes (PAH, SLC22A5, MMACHC, MMUT, MAT1A, MCCC2, ACADM, ACAD8), 35 novel variants and some genotype-biochemical phenotype associations were identified.
CONCLUSIONS: A total of 28 types of IEMs were identified, with an overall incidence of 1: 3000 in Shanghai,
China. Our study offered clinical guidance for the implementation of MS/MS-based NBS and genetic counseling for IEMs in this city.