Outcome of later-onset Pompe disease identified through newborn screening

Abstract BACKGROUND Deficiency of the lysosomal enzyme acid α-glucosidase (GAA) causes Pompe disease. Newborn screening for Pompe disease is ongoing, and improved methods for distinguishing affected patients from those with pseudodeficiency, especially in the Asian population, would substantially reduce the number of patient referrals for clinical follow-up. METHODS We measured the enzymatic activity of GAA in dried blood spots on newborn screening cards (DBS) using a tandem mass spectrometry (MS/MS) assay. The assay displayed a relatively large analytical range compared to the fluorimetric assay with 4-methylumbelliferyl-α-glucoside. DBS from newborns confirmed to have infantile-onset Pompe disease (IOPD, n = 11) or late-onset Pompe disease (LOPD) (n = 12) and those from patients bearing pseudodeficiency alleles with or without Pompe mutations, or Pompe disease carriers (n = 230) were studied. RESULTS With use of the MS/MS GAA assay in DBS, 96% of the pseudodeficiency newborns and all of the Pompe disease carriers were well separated from the IOPD and LOPD newborns. The fluorimetric assay separated <10% of the pseudodeficiencies from the IOPD/LOPD group. CONCLUSIONS The relatively large analytical range MS/MS GAA assay but not the fluorimetric assay in DBS provides a robust approach to reduce the number of referrals and should dramatically facilitate newborn screening of Pompe disease.

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Newborn screening for pompe disease? a qualitative study exploring professional views

BMC Pediatrics ◽

10.1186/1471-2431-14-203 ◽

2014 ◽

Vol 14 (1) ◽

Cited By ~ 5

Author(s):

Carla G van El ◽

Tessel Rigter ◽

Arnold JJ Reuser ◽

Ans T van der Ploeg ◽

Stephanie S Weinreich ◽

...

Keyword(s):

Qualitative Study ◽

Newborn Screening ◽

Pompe Disease

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Newborn screening for Pompe disease with dried blood spots in a Japanese region: a pilot study

Molecular Genetics and Metabolism ◽

10.1016/j.ymgme.2013.12.183 ◽

2014 ◽

Vol 111 (2) ◽

pp. S79

Author(s):

Ken Momosaki ◽

Shirou Matsumoto ◽

Kimitoshi Nakamura ◽

Hiroshi Mitsubuchi ◽

Toshika Okumiya ◽

...

Keyword(s):

Pilot Study ◽

Newborn Screening ◽

Pompe Disease ◽

Dried Blood Spots ◽

Blood Spots

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Introduction to the Newborn Screening, Diagnosis, and Treatment for Pompe Disease Guidance Supplement

PEDIATRICS ◽

10.1542/peds.2016-0280b ◽

2017 ◽

Vol 140 (Supplement 1) ◽

pp. S1-S3 ◽

Cited By ~ 5

Author(s):

Priya S. Kishnani ◽

Wuh-Liang Hwu ◽

Keyword(s):

Newborn Screening ◽

Pompe Disease ◽

Diagnosis And Treatment

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Baseline Urinary Glucose Tetrasaccharide Concentrations in Patients with Infantile- and Late-Onset Pompe Disease Identified by Newborn Screening

JIMD Reports - JIMD Reports, Volume 19 ◽

10.1007/8904_2014_366 ◽

2014 ◽

pp. 67-73 ◽

Cited By ~ 14

Author(s):

Yin-Hsiu Chien ◽

Jennifer L. Goldstein ◽

Wuh-Liang Hwu ◽

P. Brian Smith ◽

Ni-Chung Lee ◽

...

Keyword(s):

Newborn Screening ◽

Pompe Disease ◽

Late Onset ◽

Urinary Glucose ◽

Glucose Tetrasaccharide

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Evolving challenges in the era of newborn screening for Pompe disease

Molecular Genetics and Metabolism ◽

10.1016/j.ymgme.2018.12.123 ◽

2019 ◽

Vol 126 (2) ◽

pp. S54-S55

Author(s):

Lauren B. Flueckinger ◽

Priya S. Kishnani

Keyword(s):

Newborn Screening ◽

Pompe Disease

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Lessons Learned from Pompe Disease Newborn Screening and Follow-up

International Journal of Neonatal Screening ◽

10.3390/ijns6010011 ◽

2020 ◽

Vol 6 (1) ◽

pp. 11

Author(s):

Tracy L. Klug ◽

Lori B. Swartz ◽

Jon Washburn ◽

Candice Brannen ◽

Jami L. Kiesling

Keyword(s):

Newborn Screening ◽

Pompe Disease ◽

Human Services ◽

Lessons Learned ◽

Lysosomal Storage ◽

Health And Human Services ◽

Disease Phenotypes ◽

Department Of Health ◽

The World

In 2015, Pompe disease became the first lysosomal storage disorder to be recommended for universal newborn screening by the Secretary of the U.S. Department of Health and Human Services. Newborn screening for Pompe has been implemented in 20 states and several countries across the world. The rates of later-onset disease phenotypes for Pompe and pseudodeficiency alleles are higher than initially anticipated, and these factors must be considered during Pompe disease newborn screening. This report presents an overview of six years of data from the Missouri State Public Health Laboratory for Pompe disease newborn screening and follow-up.

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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

International Journal of Neonatal Screening ◽

10.3390/ijns4040041 ◽

2018 ◽

Vol 4 (4) ◽

pp. 41 ◽

Cited By ~ 6

Author(s):

Shu-Chuan Chiang ◽

Pin-Wen Chen ◽

Wuh-Liang Hwu ◽

An-Ju Lee ◽

Li-Chu Chen ◽

...

Keyword(s):

Mass Spectrometry ◽

Tandem Mass Spectrometry ◽

Newborn Screening ◽

Pompe Disease ◽

Screening Test ◽

Disease Screening ◽

Confirmatory Test ◽

Tandem Mass ◽

Lysosomal Storage ◽

Second Tier

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.

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