Gelb Michael H
Departments of Chemistry, University of Washington, Seattle, WA 98195, USA;
Departments of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Int J Neonatal Screen. 2018 Sep;4(3). doi: 10.3390/ijns4030023. Epub 2018 Jul 9.
All of the worldwide newborn screening (NBS) for lysosomal storage diseases (LSDs) is done by measurement of lysosomal enzymatic activities in dried blood spots (DBS). Substrates used for these assays are discussed. While the positive predictive value (PPV) is the gold standard for evaluating medical tests, current PPVs for NBS of LSDs cannot be used as a performance metric due to statistical sampling errors and uncertainty in the onset of disease symptoms. Instead, we consider the rate of screen positives as the only currently reliable way to compare LSD NBS results across labs worldwide. It has been suggested that the expression of enzymatic activity data as multiple-of-the-mean is a way to normalize datasets obtained using different assay platforms, so that results can be compared, and universal cutoffs can be developed. We show that this is often not the case, and normalization is currently not feasible. We summarize the recent use of pattern matching statistical analysis together with measurement of an expanded group of enzymatic activities and biomarkers to greatly reduce the number of false positives for NBS of LSDs. We provide data to show that these post-enzymatic activity assay methods are more powerful than genotype analysis for the stratification of NBS for LSDs.
全球范围内所有针对溶酶体贮积症（LSDs）的新生儿筛查（NBS）均通过检测干血斑（DBS）中的溶酶体酶活性来进行。文中讨论了用于这些检测的底物。虽然阳性预测值（PPV）是评估医学检测的金标准，但由于统计抽样误差和疾病症状出现时间的不确定性，目前LSDs的NBS的PPV不能用作性能指标。相反，我们认为筛查阳性率是目前全球各实验室比较LSDs的NBS结果的唯一可靠方法。有人提出将酶活性数据表示为均值倍数是一种对使用不同检测平台获得的数据集进行标准化的方法，以便能够比较结果并制定通用的临界值。我们表明情况往往并非如此，目前标准化并不可行。我们总结了近期模式匹配统计分析与一组扩展的酶活性和生物标志物测量方法的联合使用，以大幅减少LSDs的NBS的假阳性数量。我们提供的数据表明，这些酶活性检测后的方法在LSDs的NBS分层方面比基因分型分析更有效。
