{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T10:54:18Z","timestamp":1790679258858,"version":"4.1.0"},"reference-count":34,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,2,7]],"date-time":"2020-02-07T00:00:00Z","timestamp":1581033600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJNS"],"abstract":"<jats:p>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 \u03b1-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.<\/jats:p>","DOI":"10.3390\/ijns6010010","type":"journal-article","created":{"date-parts":[[2020,2,7]],"date-time":"2020-02-07T11:50:28Z","timestamp":1581076228000},"page":"10","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Incorporation of Second-Tier Biomarker Testing Improves the Specificity of Newborn Screening for Mucopolysaccharidosis Type I"],"prefix":"10.3390","volume":"6","author":[{"given":"Dawn S.","family":"Peck","sequence":"first","affiliation":[{"name":"Biochemical Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean M.","family":"Lacey","sequence":"additional","affiliation":[{"name":"Biochemical Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8226-615X","authenticated-orcid":false,"given":"Amy L.","family":"White","sequence":"additional","affiliation":[{"name":"Biochemical Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gisele","family":"Pino","sequence":"additional","affiliation":[{"name":"Biochemical Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"April L.","family":"Studinski","sequence":"additional","affiliation":[{"name":"Biochemical Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Fisher","sequence":"additional","affiliation":[{"name":"Division of Pediatric Genetics, Metabolism and Genomic Medicine, Department of Pediatrics, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayesha","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Division of Pediatric Genetics, Metabolism and Genomic Medicine, Department of Pediatrics, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Spencer","sequence":"additional","affiliation":[{"name":"Division of Genetic, Genomic and Metabolic Disorders, Children\u2019s Hospital of Michigan, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Viall","sequence":"additional","affiliation":[{"name":"Rare Disease Institute, Children\u2019s National Health System, Washington, DC 20010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Shallow","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics and Genomic Medicine, Monroe Carell Jr. Children\u2019s Hospital at Vanderbilt, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Siemon","sequence":"additional","affiliation":[{"name":"Division of Genetic and Genomic Medicine, Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Austin","family":"Hamm","sequence":"additional","affiliation":[{"name":"Pediatric Genetics, East Tennessee Children\u2019s Hospital, Knoxville, TN 37916, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brianna K.","family":"Murray","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics and Metabolism, Children\u2019s Hospital of the King\u2019s Daughters, Norfolk, VA 23507, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5097-9865","authenticated-orcid":false,"given":"Kelly L.","family":"Jones","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics and Metabolism, Children\u2019s Hospital of the King\u2019s Daughters, Norfolk, VA 23507, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitar","family":"Gavrilov","sequence":"additional","affiliation":[{"name":"Biochemical Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7147-5527","authenticated-orcid":false,"given":"Devin","family":"Oglesbee","sequence":"additional","affiliation":[{"name":"Biochemical Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimiyo","family":"Raymond","sequence":"additional","affiliation":[{"name":"Biochemical Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dietrich","family":"Matern","sequence":"additional","affiliation":[{"name":"Biochemical Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piero","family":"Rinaldo","sequence":"additional","affiliation":[{"name":"Biochemical Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Tortorelli","sequence":"additional","affiliation":[{"name":"Biochemical Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1093\/clinchem\/47.4.780","article-title":"Diagnosis of alpha-L-iduronidase deficiency in dried blood spots on filter paper: The possibility of newborn diagnosis","volume":"47","author":"Chamoles","year":"2001","journal-title":"Clin. 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