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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Format: | Article |
Language: | English |
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MDPI AG
2020-02-01
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Series: | International Journal of Neonatal Screening |
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Online Access: | https://www.mdpi.com/2409-515X/6/1/10 |
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doaj-d1951ec02fb74365a4d7fe391d671752 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Dawn S. Peck Jean M. Lacey Amy L. White Gisele Pino April L. Studinski Rachel Fisher Ayesha Ahmad Linda Spencer Sarah Viall Natalie Shallow Amy Siemon J. Austin Hamm Brianna K. Murray Kelly L. Jones Dimitar Gavrilov Devin Oglesbee Kimiyo Raymond Dietrich Matern Piero Rinaldo Silvia Tortorelli |
spellingShingle |
Dawn S. Peck Jean M. Lacey Amy L. White Gisele Pino April L. Studinski Rachel Fisher Ayesha Ahmad Linda Spencer Sarah Viall Natalie Shallow Amy Siemon J. Austin Hamm Brianna K. Murray Kelly L. Jones Dimitar Gavrilov Devin Oglesbee Kimiyo Raymond Dietrich Matern Piero Rinaldo Silvia Tortorelli Incorporation of Second-Tier Biomarker Testing Improves the Specificity of Newborn Screening for Mucopolysaccharidosis Type I International Journal of Neonatal Screening newborn screening mps i second-tier testing gags biomarkers postanalytical interpretation |
author_facet |
Dawn S. Peck Jean M. Lacey Amy L. White Gisele Pino April L. Studinski Rachel Fisher Ayesha Ahmad Linda Spencer Sarah Viall Natalie Shallow Amy Siemon J. Austin Hamm Brianna K. Murray Kelly L. Jones Dimitar Gavrilov Devin Oglesbee Kimiyo Raymond Dietrich Matern Piero Rinaldo Silvia Tortorelli |
author_sort |
Dawn S. Peck |
title |
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_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_sort |
incorporation of second-tier biomarker testing improves the specificity of newborn screening for mucopolysaccharidosis type i |
publisher |
MDPI AG |
series |
International Journal of Neonatal Screening |
issn |
2409-515X |
publishDate |
2020-02-01 |
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 <i>IDUA</i> 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. |
topic |
newborn screening mps i second-tier testing gags biomarkers postanalytical interpretation |
url |
https://www.mdpi.com/2409-515X/6/1/10 |
work_keys_str_mv |
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doaj-d1951ec02fb74365a4d7fe391d6717522020-11-25T00:36:20ZengMDPI AGInternational Journal of Neonatal Screening2409-515X2020-02-01611010.3390/ijns6010010ijns6010010Incorporation of Second-Tier Biomarker Testing Improves the Specificity of Newborn Screening for Mucopolysaccharidosis Type IDawn S. Peck0Jean M. Lacey1Amy L. White2Gisele Pino3April L. Studinski4Rachel Fisher5Ayesha Ahmad6Linda Spencer7Sarah Viall8Natalie Shallow9Amy Siemon10J. Austin Hamm11Brianna K. Murray12Kelly L. Jones13Dimitar Gavrilov14Devin Oglesbee15Kimiyo Raymond16Dietrich Matern17Piero Rinaldo18Silvia Tortorelli19Biochemical Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USABiochemical Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USABiochemical Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USABiochemical Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USABiochemical Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USADivision of Pediatric Genetics, Metabolism and Genomic Medicine, Department of Pediatrics, University of Michigan, Ann Arbor, MI 48109, USADivision of Pediatric Genetics, Metabolism and Genomic Medicine, Department of Pediatrics, University of Michigan, Ann Arbor, MI 48109, USADivision of Genetic, Genomic and Metabolic Disorders, Children’s Hospital of Michigan, Detroit, MI 48201, USARare Disease Institute, Children’s National Health System, Washington, DC 20010, USADivision of Medical Genetics and Genomic Medicine, Monroe Carell Jr. Children’s Hospital at Vanderbilt, Nashville, TN 37232, USADivision of Genetic and Genomic Medicine, Nationwide Children’s Hospital, Columbus, OH 43205, USAPediatric Genetics, East Tennessee Children’s Hospital, Knoxville, TN 37916, USADivision of Medical Genetics and Metabolism, Children’s Hospital of the King’s Daughters, Norfolk, VA 23507, USADivision of Medical Genetics and Metabolism, Children’s Hospital of the King’s Daughters, Norfolk, VA 23507, USABiochemical Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USABiochemical Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USABiochemical Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USABiochemical Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USABiochemical Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USABiochemical Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USAEnzyme-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 <i>IDUA</i> 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.https://www.mdpi.com/2409-515X/6/1/10newborn screeningmps isecond-tier testinggagsbiomarkerspostanalytical interpretation |