新的测试可以确保患有严重遗传疾病的新生儿得到必要的治疗
![Sample preparation workflow used to investigate reducing and maleimide derivatizing agents. In all analyses, 3.2 mm DBSs of quality control materials, proficiency materials, and residual clinical specimens were punched into 96-well plates. Arrows (stemming from “Experiments using...”) indicate where the first-tier screening method was modified to investigate reducing agents and maleimide derivatizing agents. DBSs were extracted using 100 µL WISS containing ISs for amino acids, acylcarnitines, nucleotides, homocystine (dHcy- 2 H 8 ), and other biomarkers, along with formic acid and hydrazine hydrate. A mock WISS containing dHcy- 2 H 8 along with formic acid and hydrazine hydrate was also used to investigate the presence of interferences from IS. In experiments using DTT, 12 µL of a DTT solution was added to the DBS containing WISS, then incubated for 45 min at 45°C. In experiments using TCEP, the DBS and WISS were incubated for 45 min at 45°C, then TCEP was added to the DBS extract solution and shaken for 5 min at room temperature. Sample extracts were then transferred, dried under nitrogen gas, and the DBS extracts were resuspended in 40 µL of a maleimide solution before being shaken for 5 min at room temperature. Maleimide treated extracts were then dried. Non-butyl ester extracts were resuspended in mobile phase, then analyzed by FIA–MS/MS) In butyl ester-derivatized analyses, DBS extracts were resuspended in acidified butanol, then placed in an oven for 20 min. Butylated DBS extracts were then dried, resuspended in mobile phase, and then analyzed by FIA–MS/MS. Credit: Clinical Chemistry (2023). DOI: 10.1093/clinchem/hvad007 一项新的测试可以确保患有严重遗传疾病的新生儿得到必要的治疗](https://scx1.b-cdn.net/csz/news/800a/2023/a-novel-test-could-mak.jpg)
科学家已经开发出一种测试方法,可以大大提高患有同型半胱氨酸尿症(HCU)的婴儿的生活质量。HCU是一种先天性疾病,如果不及早治疗,会导致严重的并发症。研究证明了这种测试的有效性今天发表在临床化学.
HCU阻碍婴儿代谢的能力氨基酸蛋氨酸它是许多蛋白质的组成部分,比如母乳中的蛋白质。这会导致蛋氨酸和另一种被称为同型半胱氨酸的氨基酸水平的病理性增加,如果不及时治疗,会导致严重的并发症。这些并发症包括眼睛和骨骼问题、血管异常和智力障碍。
好消息是,早期发现和治疗HCU可以预防这些并发症。鉴于此,自2006年以来,美国卫生与公众服务部已将HCU列入新生儿应筛查的疾病清单。然而,目前的测试只测量蛋氨酸水平,当新生儿筛查时,蛋氨酸水平通常仍然很低。因此,据估计,这些测试漏检了大约50%的HCU病例,这些病例有很高的风险得不到治疗。
为了解决这一问题,由疾病控制和预防中心的Konstantinos Petritis博士领导的一组研究人员开发并验证了一种通过测量同型半胱氨酸水平来检测HCU的新生儿筛查测试。在患有HCU的婴儿中,同型半胱氨酸水平通常在蛋氨酸水平之前上升,并且几乎总是在出生后的头几天进行新生儿筛查时上升,这使得同型半胱氨酸成为这种疾病更好的早期标志物。
为了评估该测试的性能,Petritis的团队用它来筛选已经接受诊断的婴儿的残余新生儿筛查样本。这些样本中有100个来自健康患者;50例来自hcu阴性的接受全肠外营养(TPN)的婴儿早产儿在新生儿重症监护室;2例hcu阳性患者。
该测试成功地区分了健康和hcu阳性样本。它还准确地将TPN样本分类为HCU阴性,这是值得注意的,因为蛋氨酸测试HCU的另一个问题是它们会产生假阳性在接受TPN的婴儿中
Petritis说:“在这里,我们提出了唯一的流动注射分析-串联质谱一级新生儿筛查方法,可以直接从干燥的血点中量化总同型半胱氨酸。”
“总的筛选能力同型半胱氨酸在一线新生儿筛查是降低HCU假阴性率的重要一步,这将使早期识别和干预能够降低HCU相关的发病率和死亡率。”
更多信息:C Austin Pickens等人,使用选择性硫醇衍生化将同型半胱氨酸多路复用到新生儿筛查的一级质谱分析,临床化学(2023)。DOI: 10.1093 / clinchem / hvad007