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Int. J. Neonatal Screen. 2019, 5(1), 1; https://doi.org/10.3390/ijns5010001

Newborn Screening for Lysosomal Storage Disorders: Methodologies for Measurement of Enzymatic Activities in Dried Blood Spots

1
Departments of Chemistry and Biochemistry, University of Washington, Seattle, WA 98195, USA
2
Newborn Screening and Metabolic Diagnostics Unit, Hamburg University Medical Center, 20246 Hamburg, Germany
3
Head Biochemical Genetics, Directorate of Genetics & Molecular Pathology, SA Pathology at the Women’s & Children’s Hospital, North Adelaide SA 5006, Australia
4
Head Reference Laboratory for Neonatal Screening, Center for Health Protection, National Institute for Public Health and the Environment (RIVM), P. O. Box 1, 3720 BA Bilthoven, The Netherlands
*
Author to whom correspondence should be addressed.
Received: 26 November 2018 / Accepted: 19 December 2018 / Published: 21 December 2018
(This article belongs to the Special Issue Newborn Screening for Lysosomal Storage Disorders)
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Abstract

All worldwide newborn screening (NBS) for lysosomal storage diseases (LSDs) is performed as a first-tier test by measurement of lysosomal enzymatic activities in dried blood spots (DBS). The currently two available methodologies used for measurement of enzymatic activities are tandem mass spectrometry (MS/MS) and digital microfluidics fluorimetry (DMF-F). In this chapter we summarize the workflows for the two platforms. Neither platform is fully automated, but the relative ease of workflow will be dependent upon the specific operation of each newborn screening laboratory on a case-by-case basis. We provide the screen positive rate (the number of below cutoff newborns per 100,000 newborns) from all NBS laboratories worldwide carrying out MS/MS-based NBS of one or more LSDs. The analytical precision of the MS/MS method is higher than that for DMF-F as shown by analysis of a common set of quality control DBS by the Centers for Disease Control and Prevention (CDC). Both the MS/MS and DMF-F platforms enable multiplexing of the LSD enzymes. An advantage of MS/MS over DMF-F is the ability to include assays of enzymatic activities and biomarkers for which no fluorimetric methods exist. Advantages of DMF-F over MS/MS are: (1) simple to use technology with same-day turn-around time for the lysosomal enzymes with the fastest rates compared to MS/MS requiring overnight analytical runs.; (2) the DMF-F instrumentation, because of its simplicity, requires less maintenance than the MS/MS platform. View Full-Text
Keywords: newborn screening; lysosomal storage diseases; cutoff values; tandem mass spectrometry; diagnosis; dried blood spots; enzymatic activity assays newborn screening; lysosomal storage diseases; cutoff values; tandem mass spectrometry; diagnosis; dried blood spots; enzymatic activity assays
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Gelb, M.H.; Lukacs, Z.; Ranieri, E.; Schielen, P.C.J.I. Newborn Screening for Lysosomal Storage Disorders: Methodologies for Measurement of Enzymatic Activities in Dried Blood Spots. Int. J. Neonatal Screen. 2019, 5, 1.

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Int. J. Neonatal Screen. EISSN 2409-515X Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
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