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

doi:10.3390/ijns6010010

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

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Biochemical Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA

Division of Pediatric Genetics, Metabolism and Genomic Medicine, Department of Pediatrics, University of Michigan, Ann Arbor, MI 48109, USA

Division of Genetic, Genomic and Metabolic Disorders, Children’s Hospital of Michigan, Detroit, MI 48201, USA

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Rare Disease Institute, Children’s National Health System, Washington, DC 20010, USA

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Division of Medical Genetics and Genomic Medicine, Monroe Carell Jr. Children’s Hospital at Vanderbilt, Nashville, TN 37232, USA

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Division of Genetic and Genomic Medicine, Nationwide Children’s Hospital, Columbus, OH 43205, USA

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Pediatric Genetics, East Tennessee Children’s Hospital, Knoxville, TN 37916, USA

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Division of Medical Genetics and Metabolism, Children’s Hospital of the King’s Daughters, Norfolk, VA 23507, USA

Authors to whom correspondence should be addressed.

Int. J. Neonatal Screen. 2020, 6(1), 10; https://doi.org/10.3390/ijns6010010

Received: 7 January 2020 / Revised: 30 January 2020 / Accepted: 5 February 2020 / Published: 7 February 2020

(This article belongs to the Special Issue CLIR Applications for Newborn Screening)

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Abstract

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. View Full-Text

Keywords: newborn screening; MPS I; second-tier testing; GAGs; biomarkers; postanalytical interpretation

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MDPI and ACS Style

Peck, D.S.; Lacey, J.M.; White, A.L.; Pino, G.; Studinski, A.L.; Fisher, R.; Ahmad, A.; Spencer, L.; Viall, S.; Shallow, N.; Siemon, A.; Hamm, J.A.; Murray, B.K.; Jones, K.L.; Gavrilov, D.; Oglesbee, D.; Raymond, K.; Matern, D.; Rinaldo, P.; Tortorelli, S. Incorporation of Second-Tier Biomarker Testing Improves the Specificity of Newborn Screening for Mucopolysaccharidosis Type I. Int. J. Neonatal Screen. 2020, 6, 10. https://doi.org/10.3390/ijns6010010

AMA Style

Peck DS, Lacey JM, White AL, Pino G, Studinski AL, Fisher R, Ahmad A, Spencer L, Viall S, Shallow N, Siemon A, Hamm JA, Murray BK, Jones KL, Gavrilov D, Oglesbee D, Raymond K, Matern D, Rinaldo P, Tortorelli S. Incorporation of Second-Tier Biomarker Testing Improves the Specificity of Newborn Screening for Mucopolysaccharidosis Type I. International Journal of Neonatal Screening. 2020; 6(1):10. https://doi.org/10.3390/ijns6010010

Chicago/Turabian Style

Peck, Dawn S., 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, and Silvia Tortorelli. 2020. "Incorporation of Second-Tier Biomarker Testing Improves the Specificity of Newborn Screening for Mucopolysaccharidosis Type I" International Journal of Neonatal Screening 6, no. 1: 10. https://doi.org/10.3390/ijns6010010

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