Cargando…

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

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 spectromet...

Descripción completa

Detalles Bibliográficos
Autores principales: Gelb, Michael H., Lukacs, Zoltan, Ranieri, Enzo, Schielen, Peter C. J. I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6448570/
https://www.ncbi.nlm.nih.gov/pubmed/30957052
http://dx.doi.org/10.3390/ijns5010001
_version_ 1783408719192653824
author Gelb, Michael H.
Lukacs, Zoltan
Ranieri, Enzo
Schielen, Peter C. J. I.
author_facet Gelb, Michael H.
Lukacs, Zoltan
Ranieri, Enzo
Schielen, Peter C. J. I.
author_sort Gelb, Michael H.
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6448570
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-64485702019-04-04 Newborn Screening for Lysosomal Storage Disorders: Methodologies for Measurement of Enzymatic Activities in Dried Blood Spots Gelb, Michael H. Lukacs, Zoltan Ranieri, Enzo Schielen, Peter C. J. I. Int J Neonatal Screen Review 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. MDPI 2018-12-21 /pmc/articles/PMC6448570/ /pubmed/30957052 http://dx.doi.org/10.3390/ijns5010001 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Gelb, Michael H.
Lukacs, Zoltan
Ranieri, Enzo
Schielen, Peter C. J. I.
Newborn Screening for Lysosomal Storage Disorders: Methodologies for Measurement of Enzymatic Activities in Dried Blood Spots
title Newborn Screening for Lysosomal Storage Disorders: Methodologies for Measurement of Enzymatic Activities in Dried Blood Spots
title_full Newborn Screening for Lysosomal Storage Disorders: Methodologies for Measurement of Enzymatic Activities in Dried Blood Spots
title_fullStr Newborn Screening for Lysosomal Storage Disorders: Methodologies for Measurement of Enzymatic Activities in Dried Blood Spots
title_full_unstemmed Newborn Screening for Lysosomal Storage Disorders: Methodologies for Measurement of Enzymatic Activities in Dried Blood Spots
title_short Newborn Screening for Lysosomal Storage Disorders: Methodologies for Measurement of Enzymatic Activities in Dried Blood Spots
title_sort newborn screening for lysosomal storage disorders: methodologies for measurement of enzymatic activities in dried blood spots
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6448570/
https://www.ncbi.nlm.nih.gov/pubmed/30957052
http://dx.doi.org/10.3390/ijns5010001
work_keys_str_mv AT gelbmichaelh newbornscreeningforlysosomalstoragedisordersmethodologiesformeasurementofenzymaticactivitiesindriedbloodspots
AT lukacszoltan newbornscreeningforlysosomalstoragedisordersmethodologiesformeasurementofenzymaticactivitiesindriedbloodspots
AT ranierienzo newbornscreeningforlysosomalstoragedisordersmethodologiesformeasurementofenzymaticactivitiesindriedbloodspots
AT schielenpetercji newbornscreeningforlysosomalstoragedisordersmethodologiesformeasurementofenzymaticactivitiesindriedbloodspots