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. 2018 Dec 18;4(4):41.
doi: 10.3390/ijns4040041. eCollection 2018 Dec.

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

Shu-Chuan Chiang  1 , Pin-Wen Chen  1 , Wuh-Liang Hwu  1   2   3 , An-Ju Lee  1 , Li-Chu Chen  1 , Ni-Chung Lee  1   2   3 , Li-Yan Chiou  1 , Yin-Hsiu Chien  1   2   3
Affiliations

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

Shu-Chuan Chiang et al. Int J Neonatal Screen. .

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.

Keywords: Fabry newborn screening; Gaucher newborn screening; Pompe newborn screening; accuracy; tandem mass spectrometry.

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Conflict of interest statement

Conflicts of InterestThe authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Distribution of screening acid α-glucosidase (GAA) activity in negatives, false positives, and patients. Whiskers: 1–99th percentile; box: 25–75th percentile; line in box: median; diamond in patients: IOPD; solid dots in patients: suspect LOPD.
Figure 2
Figure 2
Distribution of screening acid α-galactosidase (GLA) activity in negatives, false positives, and patients. Whiskers: 1–99th percentile; box: 25–75th percentile; line in box: median; Diamond in patients: classic mutation; solid dots in patients: suspect type 1 mutation or confirm type 2 mutations; hollow squares in patients: c.636 + 919G>A mutation.
See this image and copyright information in PMC

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