{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:02:15Z","timestamp":1791259335282,"version":"4.1.0"},"reference-count":15,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,10,14]],"date-time":"2020-10-14T00:00:00Z","timestamp":1602633600000},"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>Mucopolysaccharidosis Type II (MPS II), also known as Hunter syndrome, is a lysosomal storage disorder (LSD) caused by a deficiency of the lysosomal enzyme iduronate-2-sulfatase (IDS). MPS II satisfies all criteria defined by the Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC) for inclusion in the Recommended Uniform Screening Panel (RUSP) for newborn screening, apart from the fact that only minimal prospective population screening data are available. This report details the analytical validation, clinical validation, and implementation of a fluorometric assay for measurement of IDS activity in newborn dried blood spot (DBS) specimens at the Missouri State Public Health Laboratory (MSPHL). The assay is performed in a microwell plate format requiring approximately 15 min of hands-on time per plate and an incubation time of two hours. The analytical validation of this assay included linearity, analytical sensitivity, precision, and carry-over testing. Clinical validation was completed using more than 5000 deidentified presumptive normal newborn DBS specimens as well as seven specimens from patients known to be affected with MPS II. Following validation, MSPHL began prospective screening using the IDS assay on 1 November 2018. In the first 18 months of screening (to 30 June 2020), 146,954 specimens were prospectively screened using the method. Two newborns were identified with severe Hunter syndrome and the assay had a presumptive positive rate of 0.022%.<\/jats:p>","DOI":"10.3390\/ijns6040079","type":"journal-article","created":{"date-parts":[[2020,10,14]],"date-time":"2020-10-14T08:59:22Z","timestamp":1602665962000},"page":"79","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Validation and Implementation of a Highly Sensitive and Efficient Newborn Screening Assay for Mucopolysaccharidosis Type II"],"prefix":"10.3390","volume":"6","author":[{"given":"Heather","family":"Bilyeu","sequence":"first","affiliation":[{"name":"Missouri State Public Health Laboratory, 101 N. Chestnut Street, PO Box 570, Jefferson City, MO 65102-0570, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0150-5185","authenticated-orcid":false,"given":"Jon","family":"Washburn","sequence":"additional","affiliation":[{"name":"Baebies, Inc., PO Box 14403, Durham, NC 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lacey","family":"Vermette","sequence":"additional","affiliation":[{"name":"Missouri State Public Health Laboratory, 101 N. Chestnut Street, PO Box 570, Jefferson City, MO 65102-0570, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy","family":"Klug","sequence":"additional","affiliation":[{"name":"Missouri State Public Health Laboratory, 101 N. Chestnut Street, PO Box 570, Jefferson City, MO 65102-0570, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,14]]},"reference":[{"key":"ref_1","unstructured":"(2020, October 12). Secretary of Health and Human Services Recommendation to Add Pompe Disease to the RUSP, Available online: https:\/\/www.hrsa.gov\/sites\/default\/files\/hrsa\/advisory-committees\/heritable-disorders\/reports-recommendations\/letter-to-sec-pompe.pdf."},{"key":"ref_2","unstructured":"(2020, October 12). Secretary of Health and Human Services Recommendation to Add MPS I to the RUSP, Available online: https:\/\/www.hrsa.gov\/sites\/default\/files\/hrsa\/advisory-committees\/heritable-disorders\/reports-recommendations\/secretary-final-response-mpsi-rusp.pdf."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1097\/ANC.0000000000000569","article-title":"Hunter Syndrome: Is It Time to Make It Part of Newborn Screening?","volume":"18","author":"Joseph","year":"2018","journal-title":"Adv. Neonatal Care"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s13052-018-0550-5","article-title":"Mucopolysaccharidoses: Early diagnostic signs in infants and children","volume":"44","author":"Galimberti","year":"2018","journal-title":"Ital. J. Pediatr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"861","DOI":"10.2174\/138920111795542714","article-title":"Mucopolysaccharidosis Type II (Hunter Syndrome): Clinical Picture and Treatment","volume":"12","author":"Beck","year":"2011","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.ymgmr.2015.03.011","article-title":"Enzymatic replacement therapy for Hunter disease: Up to 9 years experience with 17 patients","volume":"3","author":"Parini","year":"2015","journal-title":"Mol. Genet. Metab. Reports"},{"key":"ref_7","first-page":"S56","article-title":"Clinical outcomes after 3 years of idursulfase treatment in patients with MPS II: Data from the Hunter Outcome Survey (HOS)","volume":"1","author":"Giugliani","year":"2017","journal-title":"Mol. Genet. Metab."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/8904_2018_104","article-title":"Effectiveness of early hematopoietic stem cell transplantation in preventing neurocognitive decline in mucopolysaccharidosis type ii: A case series","volume":"Volume 41","author":"Selvanathan","year":"2018","journal-title":"JIMD Reports"},{"key":"ref_9","first-page":"62","article-title":"Early hematopoietic stem cell transplantation in a patient with severe mucopolysaccharidosis II: A 7 years follow-up","volume":"12","author":"Barth","year":"2017","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"88","DOI":"10.3345\/kjp.2012.55.3.88","article-title":"A study of the relationship between clinical phenotypes and plasma iduronate-2-sulfatase enzyme activities in Hunter syndrome patients","volume":"55","author":"Lee","year":"2012","journal-title":"Korean J. Pediatr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1080\/21678707.2017.1296761","article-title":"Presentation and treatments for Mucopolysaccharidosis Type II (MPS II; Hunter Syndrome)","volume":"5","author":"Stapleton","year":"2017","journal-title":"Expert Opin. Orphan Drugs"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.jpeds.2014.09.023","article-title":"Lysosomal storage disorder screening implementation: Findings from the first six months of full population pilot testing in Missouri","volume":"166","author":"Hopkins","year":"2015","journal-title":"J. Pediatr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1001\/jamapediatrics.2018.0263","article-title":"Incidence of 4 lysosomal storage disorders from 4 years of newborn screening","volume":"172","author":"Hopkins","year":"2018","journal-title":"JAMA Pediatr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"S34","DOI":"10.1016\/j.ymgme.2018.12.067","article-title":"Newborn screening for mucopolysaccharidosis type II (MPS II) in Illinois: The first year\u2019s experience","volume":"126","author":"Burton","year":"2019","journal-title":"Mol. Genet. Metab."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1186\/s13023-018-0816-4","article-title":"Status of newborn screening and follow up investigations for Mucopolysaccharidoses I and II in Taiwan","volume":"13","author":"Chuang","year":"2018","journal-title":"Orphanet J. Rare Dis."}],"container-title":["International Journal of Neonatal Screening"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2409-515X\/6\/4\/79\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:20:58Z","timestamp":1760178058000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2409-515X\/6\/4\/79"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,14]]},"references-count":15,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["ijns6040079"],"URL":"https:\/\/doi.org\/10.3390\/ijns6040079","relation":{},"ISSN":["2409-515X"],"issn-type":[{"value":"2409-515X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,14]]}}}