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New Advances for Newborn Screening of Inborn Errors of Metabolism by Capillary Electrophoresis-Mass Spectrometry (CE-MS)

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Book cover Clinical Applications of Capillary Electrophoresis

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1972))

Abstract

Expanded newborn screening of inborn errors of metabolism (IEM) based on tandem mass spectrometry (MS/MS) technology is one of the most successful preventative healthcare initiatives for presymptomatic diagnosis and treatment of rare yet treatable genetic diseases in the population. However, confirmatory testing of presumptive screen-positive cases is required using high efficiency separations for improved specificity in order to improve the positive predictive value (PPV) for certain classes of IEMs. Here, we describe recent advances using capillary electrophoresis-mass spectrometry (CE-MS) for reliable second-tier screening or confirmatory testing based on targeted analysis of amino acids, acylcarnitines, nucleosides, and other classes of polar metabolites associated with IEMs. Additionally, nontargeted metabolite profiling enables the identification of unknown biomarkers of clinical significance for other genetic diseases that are currently screened by bioassays and/or mutation panels, such as cystic fibrosis (CF). Noteworthy, CE-MS allows for resolution of isobaric/isomeric interferences without complicated sample handling that is ideal when analyzing volume-restricted biospecimens from neonates/infants, including dried blood spots and sweat specimens. New developments to improve concentration sensitivity, as well as enhance sample throughput and quality control for unambiguous confirmatory testing of IEMs will also be discussed when using multiplexed separations based on multisegment injection-CE-MS.

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Acknowledgements

The author wishes to acknowledge funding support from National Science and Engineering Research Council of Canada, Cystic Fibrosis Canada, and Genome Canada.

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Authors and Affiliations

  1. Department of Chemistry and Chemical Biology, McMaster University, Hamilton, ON, Canada

    Meera Shanmuganathan & Philip Britz-McKibbin

Authors
  1. Meera Shanmuganathan
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  2. Philip Britz-McKibbin
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Corresponding author

Correspondence to Philip Britz-McKibbin .

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Editors and Affiliations

  1. Department of Pharmaceutics, School of Pharmacy, Virginia Commonwealth University, Richmond, VA, USA

    Terry M. Phillips

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Shanmuganathan, M., Britz-McKibbin, P. (2019). New Advances for Newborn Screening of Inborn Errors of Metabolism by Capillary Electrophoresis-Mass Spectrometry (CE-MS). In: Phillips, T.M. (eds) Clinical Applications of Capillary Electrophoresis. Methods in Molecular Biology, vol 1972. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9213-3_10

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  • DOI: https://doi.org/10.1007/978-1-4939-9213-3_10

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-4939-9212-6

  • Online ISBN: 978-1-4939-9213-3

  • eBook Packages: Springer Protocols

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