Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1783570093993623552 |
---|---|
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. |
format | Online Article Text |
id | pubmed-7422968 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT peckdawns incorporationofsecondtierbiomarkertestingimprovesthespecificityofnewbornscreeningformucopolysaccharidosistypei AT laceyjeanm incorporationofsecondtierbiomarkertestingimprovesthespecificityofnewbornscreeningformucopolysaccharidosistypei AT whiteamyl incorporationofsecondtierbiomarkertestingimprovesthespecificityofnewbornscreeningformucopolysaccharidosistypei AT pinogisele incorporationofsecondtierbiomarkertestingimprovesthespecificityofnewbornscreeningformucopolysaccharidosistypei AT studinskiaprill incorporationofsecondtierbiomarkertestingimprovesthespecificityofnewbornscreeningformucopolysaccharidosistypei AT fisherrachel incorporationofsecondtierbiomarkertestingimprovesthespecificityofnewbornscreeningformucopolysaccharidosistypei AT ahmadayesha incorporationofsecondtierbiomarkertestingimprovesthespecificityofnewbornscreeningformucopolysaccharidosistypei AT spencerlinda incorporationofsecondtierbiomarkertestingimprovesthespecificityofnewbornscreeningformucopolysaccharidosistypei AT viallsarah incorporationofsecondtierbiomarkertestingimprovesthespecificityofnewbornscreeningformucopolysaccharidosistypei AT shallownatalie incorporationofsecondtierbiomarkertestingimprovesthespecificityofnewbornscreeningformucopolysaccharidosistypei AT siemonamy incorporationofsecondtierbiomarkertestingimprovesthespecificityofnewbornscreeningformucopolysaccharidosistypei AT hammjaustin incorporationofsecondtierbiomarkertestingimprovesthespecificityofnewbornscreeningformucopolysaccharidosistypei AT murraybriannak incorporationofsecondtierbiomarkertestingimprovesthespecificityofnewbornscreeningformucopolysaccharidosistypei AT joneskellyl incorporationofsecondtierbiomarkertestingimprovesthespecificityofnewbornscreeningformucopolysaccharidosistypei AT gavrilovdimitar incorporationofsecondtierbiomarkertestingimprovesthespecificityofnewbornscreeningformucopolysaccharidosistypei AT oglesbeedevin incorporationofsecondtierbiomarkertestingimprovesthespecificityofnewbornscreeningformucopolysaccharidosistypei AT raymondkimiyo incorporationofsecondtierbiomarkertestingimprovesthespecificityofnewbornscreeningformucopolysaccharidosistypei AT materndietrich incorporationofsecondtierbiomarkertestingimprovesthespecificityofnewbornscreeningformucopolysaccharidosistypei AT rinaldopiero incorporationofsecondtierbiomarkertestingimprovesthespecificityofnewbornscreeningformucopolysaccharidosistypei AT tortorellisilvia incorporationofsecondtierbiomarkertestingimprovesthespecificityofnewbornscreeningformucopolysaccharidosistypei |