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Pilot study of newborn screening for six lysosomal storage diseases using Tandem Mass Spectrometry()
BACKGROUND: There is current expansion of newborn screening (NBS) programs to include lysosomal storage disorders because of the availability of treatments that produce an optimal clinical outcome when started early in life. OBJECTIVE: To evaluate the performance of a multiplex-tandem mass spectrome...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5318163/ https://www.ncbi.nlm.nih.gov/pubmed/27238910 http://dx.doi.org/10.1016/j.ymgme.2016.05.015 |
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author | Elliott, Susan Buroker, Norman Cournoyer, Jason J. Potier, Anna M. Trometer, Joseph D. Elbin, Carole Schermer, Mack J. Kantola, Jaana Boyce, Aaron Turecek, Frantisek Gelb, Michael H. Scott, C. Ronald |
author_facet | Elliott, Susan Buroker, Norman Cournoyer, Jason J. Potier, Anna M. Trometer, Joseph D. Elbin, Carole Schermer, Mack J. Kantola, Jaana Boyce, Aaron Turecek, Frantisek Gelb, Michael H. Scott, C. Ronald |
author_sort | Elliott, Susan |
collection | PubMed |
description | BACKGROUND: There is current expansion of newborn screening (NBS) programs to include lysosomal storage disorders because of the availability of treatments that produce an optimal clinical outcome when started early in life. OBJECTIVE: To evaluate the performance of a multiplex-tandem mass spectrometry (MS/MS) enzymatic activity assay of 6 lysosomal enzymes in a NBS laboratory for the identification of newborns at risk for developing Pompe, Mucopolysaccharidosis-I (MPS-I), Fabry, Gaucher, Niemann Pick-A/B, and Krabbe diseases. METHODS AND RESULTS: Enzyme activities (acid α-glucosidase (GAA), galactocerebrosidase (GALC), glucocerebrosidase (GBA), α-galactosidase A (GLA), α-iduronidase (IDUA) and sphingomyeline phosphodiesterase-1 (SMPD-1)) were measured on ~43,000 de-identified dried blood spot (DBS) punches, and screen positive samples were submitted for DNA sequencing to obtain genotype confirmation of disease risk. The 6-plex assay was efficiently performed in the Washington state NBS laboratory by a single laboratory technician at the bench using a single MS/MS instrument. The number of screen positive samples per 100,000 newborns were as follows: GAA (4.5), IDUA (13.6), GLA (18.2), SMPD1 (11.4), GBA (6.8), and GALC (25.0). DISCUSSION: A 6-plex MS/MS assay for 6 lysosomal enzymes can be successfully performed in a NBS laboratory. The analytical ranges (enzyme-dependent assay response for the quality control HIGH sample divided by that for all enzyme-independent processes) for the 6-enzymes with the MS/MS is 5- to 15-fold higher than comparable fluorimetric assays using 4-methylumbelliferyl substrates. The rate of screen positive detection is consistently lower for the MS/MS assay compared to the fluorimetric assay using a digital microfluidics platform. |
format | Online Article Text |
id | pubmed-5318163 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
record_format | MEDLINE/PubMed |
spelling | pubmed-53181632017-02-20 Pilot study of newborn screening for six lysosomal storage diseases using Tandem Mass Spectrometry() Elliott, Susan Buroker, Norman Cournoyer, Jason J. Potier, Anna M. Trometer, Joseph D. Elbin, Carole Schermer, Mack J. Kantola, Jaana Boyce, Aaron Turecek, Frantisek Gelb, Michael H. Scott, C. Ronald Mol Genet Metab Article BACKGROUND: There is current expansion of newborn screening (NBS) programs to include lysosomal storage disorders because of the availability of treatments that produce an optimal clinical outcome when started early in life. OBJECTIVE: To evaluate the performance of a multiplex-tandem mass spectrometry (MS/MS) enzymatic activity assay of 6 lysosomal enzymes in a NBS laboratory for the identification of newborns at risk for developing Pompe, Mucopolysaccharidosis-I (MPS-I), Fabry, Gaucher, Niemann Pick-A/B, and Krabbe diseases. METHODS AND RESULTS: Enzyme activities (acid α-glucosidase (GAA), galactocerebrosidase (GALC), glucocerebrosidase (GBA), α-galactosidase A (GLA), α-iduronidase (IDUA) and sphingomyeline phosphodiesterase-1 (SMPD-1)) were measured on ~43,000 de-identified dried blood spot (DBS) punches, and screen positive samples were submitted for DNA sequencing to obtain genotype confirmation of disease risk. The 6-plex assay was efficiently performed in the Washington state NBS laboratory by a single laboratory technician at the bench using a single MS/MS instrument. The number of screen positive samples per 100,000 newborns were as follows: GAA (4.5), IDUA (13.6), GLA (18.2), SMPD1 (11.4), GBA (6.8), and GALC (25.0). DISCUSSION: A 6-plex MS/MS assay for 6 lysosomal enzymes can be successfully performed in a NBS laboratory. The analytical ranges (enzyme-dependent assay response for the quality control HIGH sample divided by that for all enzyme-independent processes) for the 6-enzymes with the MS/MS is 5- to 15-fold higher than comparable fluorimetric assays using 4-methylumbelliferyl substrates. The rate of screen positive detection is consistently lower for the MS/MS assay compared to the fluorimetric assay using a digital microfluidics platform. 2016-05-20 2016-08 /pmc/articles/PMC5318163/ /pubmed/27238910 http://dx.doi.org/10.1016/j.ymgme.2016.05.015 Text en This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Elliott, Susan Buroker, Norman Cournoyer, Jason J. Potier, Anna M. Trometer, Joseph D. Elbin, Carole Schermer, Mack J. Kantola, Jaana Boyce, Aaron Turecek, Frantisek Gelb, Michael H. Scott, C. Ronald Pilot study of newborn screening for six lysosomal storage diseases using Tandem Mass Spectrometry() |
title | Pilot study of newborn screening for six lysosomal storage diseases using Tandem Mass Spectrometry() |
title_full | Pilot study of newborn screening for six lysosomal storage diseases using Tandem Mass Spectrometry() |
title_fullStr | Pilot study of newborn screening for six lysosomal storage diseases using Tandem Mass Spectrometry() |
title_full_unstemmed | Pilot study of newborn screening for six lysosomal storage diseases using Tandem Mass Spectrometry() |
title_short | Pilot study of newborn screening for six lysosomal storage diseases using Tandem Mass Spectrometry() |
title_sort | pilot study of newborn screening for six lysosomal storage diseases using tandem mass spectrometry() |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5318163/ https://www.ncbi.nlm.nih.gov/pubmed/27238910 http://dx.doi.org/10.1016/j.ymgme.2016.05.015 |
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