Performance of the Four-Plex Tandem Mass Spectrometry Lysosomal Storage Disease Newborn Screening Test: The Necessity of Adding a 2nd Tier Test for Pompe Disease.

Yin-Hsiu Chien,Wuh-Liang Hwu,An-Ju Lee,Ni-Chung Lee,Li-Yan Chiou,Li-Chu Chen,Pin-Wen Chen,Shu-Chuan Chiang

doi:10.3390/ijns4040041

Abstract

Early diagnosis of lysosomal storage diseases (LSDs) through newborn screening (NBS) has been adapted widely. The National Taiwan University Hospital Newborn Screening Center launched the four-plex tandem mass spectrometry LSD newborn screening test in 2015. The test determined activities of acid α-glucosidase (GAA; Pompe), acid α-galactosidase (GLA; Fabry), acid β-glucocerebrosidase (ABG; Gaucher), and acid α-l-iduronidase (IDUA; MPS-I) in dried blood spots (DBS). Through 2017, 64,148 newborns were screened for these four LSDs. The screening algorithm includes enzyme activity/ratio as the cutoffs for the first screening test and a second-tier test for Pompe disease screening. The second-tier Pompe disease screening test measured activity inhibition by acarbose. Twenty-nine newborns required a confirmatory test; six were confirmed to have Pompe disease, and nine were confirmed to have Fabry disease. The screen-positive rate for Pompe disease was 0.031%. Therefore, in Pompe disease newborn screening, a validated 2nd tier test is necessary to decrease false positives.

Highlights

Lysosomal storage diseases (LSDs) are caused by a deficiency of one of the lysosomal acid hydrolases
After we realized the presence of a common pseudodeficiency allele in the Taiwanese population, we improved the screening algorithm by adding a 2nd tier test measuring neutral α-glucosidase (NAG) and total α-glucosidase (TAG) activities
We report our results from screening of the first 60,000 newborns using the MS/MS method to demonstrate the necessity of a 2nd tier test for Pompe disease

Summary

Introduction

Lysosomal storage diseases (LSDs) are caused by a deficiency of one of the lysosomal acid hydrolases. Because LSDs can lead to irreversible damage to the tissues and organs of affected children, screening newborns for treatable LSDs has been conducted in different populations with the goal of reducing disease-related morbidity and mortality through early treatment. After we realized the presence of a common pseudodeficiency allele in the Taiwanese population, we improved the screening algorithm by adding a 2nd tier test measuring neutral α-glucosidase (NAG) and total α-glucosidase (TAG) activities. This approach reduces the false positive rate to a recall rate of lower than 0.26% [5]

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Results

Discussion

Conclusion