Chen Chi, Zhang Chao, Wu Ding-Wen, Wang Bing-Yi, Xiao Rui, Huang Xiao-Lei, Yang Xin, Gao Zhi-Gang, Yang Ru-Lai
Department of Genetics and Metabolism, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.
National Engineering Laboratory for Key Technology of Birth Defect Control and Prevention, Screening and Diagnostic R and D Center, Hangzhou, China.
World J Pediatr. 2024 Dec;20(12):1270-1282. doi: 10.1007/s12519-024-00846-7. Epub 2024 Nov 5.
Newborn screening (NBS) for severe combined immunodeficiency (SCID), X-linked agammaglobulinemia (XLA), and spinal muscular atrophy (SMA) enables early diagnosis and intervention, significantly improving patient outcomes. Advances in real-time polymerase chain reaction (PCR) technology have been instrumental in facilitating their inclusion in NBS programs.
We employed multiplex real-time PCR to simultaneously detect T-cell receptor excision circles (TRECs), kappa-deleting recombination excision circles (KRECs), and the absence of the survival motor neuron (SMN) 1 gene in dried blood spots from 103,240 newborns in Zhejiang Province, China, between July 2021 and December 2022.
Of all the samples, 122 were requested further evaluation. After flow cytometry evaluation and/or genetic diagnostics, we identified one patient with SCID, two patients with XLA, nine patients with SMA [one of whom also had Wiskott-Aldrich Syndrome (WAS)], and eight patients with other medical conditions. The positive predictive values (PPVs) of NBS for SCID, XLA, and SMA were 2.44%, 2.78%, and 100%, respectively. The estimated prevalence rates in the Chinese population were 1 in 103,240 for SCID, 1 in 51,620 for XLA, and 1 in 11,471 for SMA.
This study represents the first large-scale screening in mainland China using a TREC/KREC/SMN1 multiplex assay, providing valuable epidemiological data. Our findings suggest that this multiplex assay is an effective screening method for SCID, XLA, and SMA, potentially supporting the universal implementation of NBS programs across China.
对重症联合免疫缺陷（SCID）、X连锁无丙种球蛋白血症（XLA）和脊髓性肌萎缩症（SMA）进行新生儿筛查可实现早期诊断和干预，显著改善患者预后。实时聚合酶链反应（PCR）技术的进步有助于将这些疾病纳入新生儿筛查项目。
我们采用多重实时PCR技术，对2021年7月至2022年12月期间中国浙江省103240名新生儿的干血斑同时检测T细胞受体切除环（TRECs）、κ链缺失重组切除环（KRECs）以及生存运动神经元（SMN）1基因的缺失情况。
在所有样本中，有122例被要求进一步评估。经过流式细胞术评估和/或基因诊断，我们鉴定出1例SCID患者、2例XLA患者、9例SMA患者[其中1例还患有威斯科特-奥尔德里奇综合征（WAS）]以及8例患有其他病症的患者。新生儿筛查对SCID、XLA和SMA的阳性预测值（PPV）分别为2.44%、2.78%和100%。中国人群中SCID的估计患病率为1/103240，XLA为1/51620，SMA为1/11471。
本研究是中国大陆首次使用TREC/KREC/SMN1多重检测法进行的大规模筛查，提供了有价值的流行病学数据。我们的研究结果表明，这种多重检测法是一种用于SCID、XLA和SMA的有效筛查方法，可能支持在中国全面实施新生儿筛查项目。
