Lysosomal Storage Disorder Screening Implementation: Findings from the First Six Months of Full Population Pilot Testing in Missouri
Lysosomal Storage Disorder Screening Implementation: Findings from the First Six Months of Full Population Pilot Testing in Missouri
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DOI：
10.1016/j.jpeds.2014.09.023
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发表时间：
2015-01-01
影响因子：
5.1
通讯作者：
Kiesling, Jami
中科院分区：
文献类型：
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作者：
Hopkins, Patrick V.;Campbell, Carlene;Kiesling, Jami
目的 评估密苏里州针对新生儿血斑使用数字微流控筛查溶酶体贮积症 (LSD) 的全州全人群试点研究的效果。 研究设计 一项使用多重荧光酶法检测密苏里州新生儿人群庞贝病、法布里病、戈谢病和 I 型粘多糖贮积症 (MPS I) 的全人群试点研究正在进行中。临时截止值是在预试点研究期间确定的。在试点研究期间，对密苏里州公共卫生实验室收到的用于常规新生儿筛查的所有新生儿干血斑进行了 4 种 LSD 筛查。确定筛查呈阳性的新生儿被转介进行确认性检测。 结果 该研究于 2013 年 1 月 11 日开始；在前 6 个月内，对 43 701 份标本进行了筛查，并鉴定出 27 名确诊为 LSD 基因型的新生儿（8 名庞贝病、1 名戈谢病、15 名法布里病和 3 名 MPS I）。这些数字对应的庞贝病检出率为 1:5463，戈谢病为 1:43 701，法布里病为 1:2913，MPS I 为 1:14 567。庞贝病的阳性预测值为 47%，其中 1 例失访；戈谢病为 10%；法布里病为 58%，其中 2 例失访；以及MPS I 为 11%，有 4 个待定。结论 密苏里州 LSD 试点研究的前 6 个月提供了验证数字微流体筛查方法有效性的机会，完善了这些 LSD 检测的截止值，并测试了婴儿转诊、随访、确认、治疗和筛查计划沟通的整个系统。
Objective To evaluate the performance of a statewide full-population pilot study in Missouri on newborn blood spots for screening of lysosomal storage disorders (LSDs) using digital microfluidics.Study design A full-population pilot study using a multiplexed fluorometric enzymatic assay to detect Pompe disease, Fabry disease, Gaucher disease, and mucopolysaccharidosis type I (MPS I) in the Missouri newborn population is ongoing. Provisional cutoff values were determined during a prepilot study. All newborn dried blood spots received at the Missouri State Public Health Laboratory for routine newborn screening were screened for the 4 LSDs during the pilot study. Newborns determined to be screen-positive were referred for confirmatory testing.Results The study commenced on January 11, 2013; during the first 6 months, 43 701 specimens were screened, and 27 newborns with a confirmed diagnosis of an LSD genotype (8 with Pompe disease, 1 with Gaucher disease, 15 with Fabry disease, and 3 with MPS I) were identified. These numbers correspond to detection rates of 1:5463 for Pompe disease, 1: 43 701 for Gaucher disease, 1:2913 for Fabry disease, and 1:14 567 for MPS I. The positive predictive values were 47% for Pompe disease with 1 lost to follow-up, 10% for Gaucher disease, 58% for Fabry disease with 2 lost to follow-up, and 11% for MPS I with 4 pending.Conclusion The first 6 months of the Missouri LSD pilot study provided the opportunity to validate the effectiveness of the digital microfluidic screening method, refine the cutoffs for detection of these LSDs, and test the entire system of infant referral, follow-up, confirmation, treatment, and screening program communication.