{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T10:21:31Z","timestamp":1787739691333,"version":"build-2784847793"},"reference-count":37,"publisher":"Walter de Gruyter GmbH","issue":"12","license":[{"start":{"date-parts":[[2020,5,20]],"date-time":"2020-05-20T00:00:00Z","timestamp":1589932800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,11,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec id=\"j_cclm-2020-0064_s_999\">\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Mucopolysaccharidosis type I (MPS I) was added to our expanded screening panel in 2015. Since then, 127,869 newborns were screened by measuring \u03b1-L-iduronidase (IDUA) enzyme activity with liquid chromatography tandem mass spectrometry (LC-MS\/MS). High false positives due to frequent pseudodeficiency alleles prompted us to develop a second-tier test to quantify glycosaminoglycan (GAG) levels in dried blood spot (DBS).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_cclm-2020-0064_s_998\">\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Heparan-sulfate (HS) and dermatan-sulfate (DS) were measured with LC-MS\/MS after methanolysis. DBSs were incubated with methanolic-HCl 3 N at 65 \u00b0C for 45 min. Chromatographic separation used an amide column with a gradient of acetonitrile and water with 10 mM ammonium acetate in a 9-min run. The method was validated for specificity, linearity, lower limit of quantification (LOQ), accuracy and precision.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_cclm-2020-0064_s_997\">\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Intra- and inter-day coefficients of variation were &lt;15% for both metabolites. Reference values in 40 healthy newborns were: HS mean 1.0 mg\/L, 0\u20133.2; DS mean 1.5 mg\/L, 0.5\u20132.7). The two confirmed newborn MPS I patients had elevated HS (4.9\u201310.4 mg\/L, n.v. &lt;3.2) and DS (7.4\u20138.8 mg\/L, n.v. &lt;2.7). Since its introduction in February 2019, the second-tier test reduced the recall rate from 0.046% to 0.006%. Among 127,869 specimens screened, the incidence was 1:63,935 live births. Both patients started enzyme replacement therapy (ERT) within 15 days of birth and one of them received allogenic hematopoietic stem cell transplantation (HSCT) at ht age of 6 months.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_cclm-2020-0064_s_996\">\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>GAGs in DBS increased the specificity of newborn screening for MPS I by reducing false-positives due to heterozygosity or pseudodeficiency. Early diagnosis and therapeutical approach has improved the outcome of our patients with MPS I.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1515\/cclm-2020-0064","type":"journal-article","created":{"date-parts":[[2020,5,26]],"date-time":"2020-05-26T17:09:51Z","timestamp":1590512991000},"page":"2063-2072","source":"Crossref","is-referenced-by-count":22,"title":["The combined use of enzyme activity and metabolite assays as a strategy for newborn screening of mucopolysaccharidosis type I"],"prefix":"10.1515","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3157-2979","authenticated-orcid":false,"given":"Giulia","family":"Polo","sequence":"first","affiliation":[{"name":"Division of Inherited Metabolic Diseases, Regional Center for Expanded Neonatal Screening Department of Women and Children\u2019s Health , University Hospital of Padova , Via Orus 2\/B , 35129 Padova , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Gueraldi","sequence":"additional","affiliation":[{"name":"Division of Inherited Metabolic Diseases, Regional Center for Expanded Neonatal Screening Department of Women and Children\u2019s Health , University Hospital of Padova , Via Orus 2\/B , 35129 Padova , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Giuliani","sequence":"additional","affiliation":[{"name":"Division of Inherited Metabolic Diseases, Regional Center for Expanded Neonatal Screening Department of Women and Children\u2019s Health , University Hospital of Padova , Via Orus 2\/B , 35129 Padova , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Rubert","sequence":"additional","affiliation":[{"name":"Division of Inherited Metabolic Diseases, Regional Center for Expanded Neonatal Screening Department of Women and Children\u2019s Health , University Hospital of Padova , Via Orus 2\/B , 35129 Padova , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Cazzorla","sequence":"additional","affiliation":[{"name":"Division of Inherited Metabolic Diseases, Regional Center for Expanded Neonatal Screening Department of Women and Children\u2019s Health , University Hospital of Padova , Via Orus 2\/B , 35129 Padova , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"Salviati","sequence":"additional","affiliation":[{"name":"Clinical Genetics Unit, Department of Women\u2019s and Children\u2019s Health , University of Padova , Padova , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Marzollo","sequence":"additional","affiliation":[{"name":"Pediatric Hematology-Oncology Unit, Department of Women\u2019s and Children\u2019s Health , University of Padova , Padova , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Biffi","sequence":"additional","affiliation":[{"name":"Pediatric Hematology-Oncology Unit, Department of Women\u2019s and Children\u2019s Health , University of Padova , Padova , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro P.","family":"Burlina","sequence":"additional","affiliation":[{"name":"Neurological Unit, St. Bassiano Hospital , Bassano del Grappa , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto B.","family":"Burlina","sequence":"additional","affiliation":[{"name":"Division of Inherited Metabolic Diseases, Regional Center for Expanded Neonatal Screening Department of Women and Children\u2019s Health , University Hospital of Padova , Via Orus 2\/B , 35129 Padova , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2020,5,20]]},"reference":[{"key":"2023033111431165145_j_cclm-2020-0064_ref_001","doi-asserted-by":"crossref","unstructured":"Muenzer J. 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