Sanders Karen A, Gavrilov Dimitar K, Oglesbee Devin, Raymond Kimiyo M, Tortorelli Silvia, Hopwood John J, Lorey Fred, Majumdar Ramanath, Kroll Charles A, McDonald Amber M, Lacey Jean M, Turgeon Coleman T, Tucker Justin N, Tang Hao, Currier Robert, Isaya Grazia, Rinaldo Piero, Matern Dietrich
Biochemical Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA.
Department of Clinical Genomics, Mayo Clinic, Rochester, MN 55905, USA.
Int J Neonatal Screen. 2020 Jun;6(2). doi: 10.3390/ijns6020044. Epub 2020 May 30.
Newborn screening for one or more lysosomal disorders has been implemented in several US states, Japan and Taiwan by multiplexed enzyme assays using either tandem mass spectrometry or digital microfluidics. Another multiplex assay making use of immunocapture technology has also been proposed. To investigate the potential variability in performance of these analytical approaches, we implemented three high-throughput screening assays for the simultaneous screening for four lysosomal disorders: Fabry disease, Gaucher disease, mucopolysaccharidosis type I, and Pompe disease. These assays were tested in a prospective comparative effectiveness study using nearly 100,000 residual newborn dried blood spot specimens. In addition, 2nd tier enzyme assays and confirmatory molecular genetic testing were employed. Post-analytical interpretive tools were created using the software Collaborative Laboratory Integrated Reports (CLIR) to determine its ability to improve the performance of each assay vs. the traditional result interpretation based on analyte-specific reference ranges and cutoffs. This study showed that all three platforms have high sensitivity, and the application of CLIR tools markedly improves the performance of each platform while reducing the need for 2nd tier testing by 66% to 95%. Moreover, the addition of disease-specific biochemical 2nd tier tests ensures the lowest false positive rates and the highest positive predictive values for any platform.
美国的几个州、日本和台湾已通过使用串联质谱或数字微流控技术的多重酶测定法，对一种或多种溶酶体疾病进行新生儿筛查。另一种利用免疫捕获技术的多重测定法也已被提出。为了研究这些分析方法在性能上的潜在差异，我们实施了三种高通量筛查测定法，用于同时筛查四种溶酶体疾病：法布里病、戈谢病、I型黏多糖贮积症和庞贝病。这些测定法在一项前瞻性比较有效性研究中进行了测试，该研究使用了近100,000份新生儿残留干血斑标本。此外，还采用了二线酶测定法和确证性分子遗传学检测。使用协作实验室综合报告（CLIR）软件创建了分析后解释工具，以确定其相对于基于分析物特异性参考范围和临界值的传统结果解释，提高每种测定法性能的能力。这项研究表明，所有三个平台都具有高灵敏度，CLIR工具的应用显著提高了每个平台的性能，同时将二线检测的需求减少了66%至95%。此外，添加疾病特异性生化二线检测可确保任何平台的假阳性率最低，阳性预测值最高。
