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Incorporation of Second-Tier Biomarker Testing Improves the Specificity of Newborn Screening for Mucopolysaccharidosis Type I

Enzyme-based newborn screening for Mucopolysaccharidosis type I (MPS I) has a high false-positive rate due to the prevalence of pseudodeficiency alleles, often resulting in unnecessary and costly follow up. The glycosaminoglycans (GAGs), dermatan sulfate (DS) and heparan sulfate (HS) are both substr...

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Autores principales: Peck, Dawn S., Lacey, Jean M., White, Amy L., Pino, Gisele, Studinski, April L., Fisher, Rachel, Ahmad, Ayesha, Spencer, Linda, Viall, Sarah, Shallow, Natalie, Siemon, Amy, Hamm, J. Austin, Murray, Brianna K., Jones, Kelly L., Gavrilov, Dimitar, Oglesbee, Devin, Raymond, Kimiyo, Matern, Dietrich, Rinaldo, Piero, Tortorelli, Silvia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7422968/
https://www.ncbi.nlm.nih.gov/pubmed/33073008
http://dx.doi.org/10.3390/ijns6010010
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author Peck, Dawn S.
Lacey, Jean M.
White, Amy L.
Pino, Gisele
Studinski, April L.
Fisher, Rachel
Ahmad, Ayesha
Spencer, Linda
Viall, Sarah
Shallow, Natalie
Siemon, Amy
Hamm, J. Austin
Murray, Brianna K.
Jones, Kelly L.
Gavrilov, Dimitar
Oglesbee, Devin
Raymond, Kimiyo
Matern, Dietrich
Rinaldo, Piero
Tortorelli, Silvia
author_facet Peck, Dawn S.
Lacey, Jean M.
White, Amy L.
Pino, Gisele
Studinski, April L.
Fisher, Rachel
Ahmad, Ayesha
Spencer, Linda
Viall, Sarah
Shallow, Natalie
Siemon, Amy
Hamm, J. Austin
Murray, Brianna K.
Jones, Kelly L.
Gavrilov, Dimitar
Oglesbee, Devin
Raymond, Kimiyo
Matern, Dietrich
Rinaldo, Piero
Tortorelli, Silvia
author_sort Peck, Dawn S.
collection PubMed
description Enzyme-based newborn screening for Mucopolysaccharidosis type I (MPS I) has a high false-positive rate due to the prevalence of pseudodeficiency alleles, often resulting in unnecessary and costly follow up. The glycosaminoglycans (GAGs), dermatan sulfate (DS) and heparan sulfate (HS) are both substrates for α-l-iduronidase (IDUA). These GAGs are elevated in patients with MPS I and have been shown to be promising biomarkers for both primary and second-tier testing. Since February 2016, we have measured DS and HS in 1213 specimens submitted on infants at risk for MPS I based on newborn screening. Molecular correlation was available for 157 of the tested cases. Samples from infants with MPS I confirmed by IDUA molecular analysis all had significantly elevated levels of DS and HS compared to those with confirmed pseudodeficiency and/or heterozygosity. Analysis of our testing population and correlation with molecular results identified few discrepant outcomes and uncovered no evidence of false-negative cases. We have demonstrated that blood spot GAGs analysis accurately discriminates between patients with confirmed MPS I and false-positive cases due to pseudodeficiency or heterozygosity and increases the specificity of newborn screening for MPS I.
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spelling pubmed-74229682020-10-15 Incorporation of Second-Tier Biomarker Testing Improves the Specificity of Newborn Screening for Mucopolysaccharidosis Type I Peck, Dawn S. Lacey, Jean M. White, Amy L. Pino, Gisele Studinski, April L. Fisher, Rachel Ahmad, Ayesha Spencer, Linda Viall, Sarah Shallow, Natalie Siemon, Amy Hamm, J. Austin Murray, Brianna K. Jones, Kelly L. Gavrilov, Dimitar Oglesbee, Devin Raymond, Kimiyo Matern, Dietrich Rinaldo, Piero Tortorelli, Silvia Int J Neonatal Screen Article Enzyme-based newborn screening for Mucopolysaccharidosis type I (MPS I) has a high false-positive rate due to the prevalence of pseudodeficiency alleles, often resulting in unnecessary and costly follow up. The glycosaminoglycans (GAGs), dermatan sulfate (DS) and heparan sulfate (HS) are both substrates for α-l-iduronidase (IDUA). These GAGs are elevated in patients with MPS I and have been shown to be promising biomarkers for both primary and second-tier testing. Since February 2016, we have measured DS and HS in 1213 specimens submitted on infants at risk for MPS I based on newborn screening. Molecular correlation was available for 157 of the tested cases. Samples from infants with MPS I confirmed by IDUA molecular analysis all had significantly elevated levels of DS and HS compared to those with confirmed pseudodeficiency and/or heterozygosity. Analysis of our testing population and correlation with molecular results identified few discrepant outcomes and uncovered no evidence of false-negative cases. We have demonstrated that blood spot GAGs analysis accurately discriminates between patients with confirmed MPS I and false-positive cases due to pseudodeficiency or heterozygosity and increases the specificity of newborn screening for MPS I. MDPI 2020-02-07 /pmc/articles/PMC7422968/ /pubmed/33073008 http://dx.doi.org/10.3390/ijns6010010 Text en © 2020 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 Article
Peck, Dawn S.
Lacey, Jean M.
White, Amy L.
Pino, Gisele
Studinski, April L.
Fisher, Rachel
Ahmad, Ayesha
Spencer, Linda
Viall, Sarah
Shallow, Natalie
Siemon, Amy
Hamm, J. Austin
Murray, Brianna K.
Jones, Kelly L.
Gavrilov, Dimitar
Oglesbee, Devin
Raymond, Kimiyo
Matern, Dietrich
Rinaldo, Piero
Tortorelli, Silvia
Incorporation of Second-Tier Biomarker Testing Improves the Specificity of Newborn Screening for Mucopolysaccharidosis Type I
title Incorporation of Second-Tier Biomarker Testing Improves the Specificity of Newborn Screening for Mucopolysaccharidosis Type I
title_full Incorporation of Second-Tier Biomarker Testing Improves the Specificity of Newborn Screening for Mucopolysaccharidosis Type I
title_fullStr Incorporation of Second-Tier Biomarker Testing Improves the Specificity of Newborn Screening for Mucopolysaccharidosis Type I
title_full_unstemmed Incorporation of Second-Tier Biomarker Testing Improves the Specificity of Newborn Screening for Mucopolysaccharidosis Type I
title_short Incorporation of Second-Tier Biomarker Testing Improves the Specificity of Newborn Screening for Mucopolysaccharidosis Type I
title_sort incorporation of second-tier biomarker testing improves the specificity of newborn screening for mucopolysaccharidosis type i
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7422968/
https://www.ncbi.nlm.nih.gov/pubmed/33073008
http://dx.doi.org/10.3390/ijns6010010
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