Klippel Claire, Park Jiwoon, Sandin Sean, Winstone Tara M L, Chen Xue, Orton Dennis, Singh Aranjeet, Hill Jonathan D, Shahbal Tareq K, Hamacher Emily, Officer Brandon, Thompson John, Duong Phi, Grotzer Tim, Hahn Si Houn
Key Proteo, Inc., Seattle, WA 98122, USA.
Alberta Precision Laboratories, Calgary, AB T2L 2K8, Canada.
Int J Neonatal Screen. 2025 Jan 10;11(1):6. doi: 10.3390/ijns11010006.
For many genetic disorders, there are no specific metabolic biomarkers nor analytical methods suitable for newborn population screening, even where highly effective preemptive treatments are available. The direct measurement of signature peptides as a surrogate marker for the protein in dried blood spots (DBSs) has been shown to successfully identify patients with Wilson Disease (WD) and three life-threatening inborn errors of immunity, X-linked agammaglobulinemia (XLA), Wiskott-Aldrich syndrome (WAS), and adenosine deaminase deficiency (ADAD). A novel proteomic-based multiplex assay to detect these four conditions from DBS using high-throughput LC-MS/MS was developed and validated. The clinical validation results showed that the assay can accurately identify patients of targeted disorders from controls. Additionally, 30,024 newborn DBS samples from the Washington State Department of Health Newborn Screening Laboratory have been screened from 2022 to 2024. One true presumptive positive case of WD was found along with three false positive cases. Five false positives for WAS were detected, but all of them were premature and/or low-birth-weight babies and four of them had insufficient DNA for confirmation. The pilot study demonstrates the feasibility and effectiveness of utilizing this multiplexed proteomic assay for newborn screening.
对于许多遗传疾病而言，即便有高效的预防性治疗方法，也没有适用于新生儿群体筛查的特定代谢生物标志物及分析方法。直接测量干血斑（DBS）中作为蛋白质替代标志物的特征肽，已被证明能成功识别威尔逊病（WD）患者以及三种危及生命的先天性免疫缺陷疾病患者，即X连锁无丙种球蛋白血症（XLA）、威斯科特-奥尔德里奇综合征（WAS）和腺苷脱氨酶缺乏症（ADAD）。开发并验证了一种基于蛋白质组学的新型多重检测方法，用于从DBS中检测这四种疾病，采用高通量液相色谱-串联质谱（LC-MS/MS）技术。临床验证结果表明，该检测方法能够准确地从对照中识别出目标疾病患者。此外，2022年至2024年期间，对华盛顿州卫生部新生儿筛查实验室的30,024份新生儿DBS样本进行了筛查。发现了1例真正的WD疑似阳性病例以及3例假阳性病例。检测到5例假阳性的WAS病例，但所有这些病例均为早产儿和/或低体重儿，其中4例DNA不足，无法进行确认。这项初步研究证明了利用这种多重蛋白质组学检测方法进行新生儿筛查的可行性和有效性。
