{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,4]],"date-time":"2025-10-04T22:10:11Z","timestamp":1759615811472,"version":"3.40.5"},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,2,10]],"date-time":"2020-02-10T00:00:00Z","timestamp":1581292800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["HD087818\u201001"],"award-info":[{"award-number":["HD087818\u201001"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JIMD Reports"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>Current newborn screening (NBS) for mucopolysaccharidosis type I (MPSI) has very high false positive rates and low positive predictive values (PPVs). To improve the accuracy of presymptomatic prediction for MPSI, we propose an NBS tool based on known biomarkers, alpha\u2010L\u2010iduronidase enzyme activity (IDUA) and level of the glycosaminoglycan (GAG) heparan sulfate (HS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We developed the NBS tool using measures from dried blood spots (DBS) of 5000 normal newborns from Gifu Prefecture, Japan. The tool's predictive accuracy was tested on the newborn DBS from these infants and from seven patients who were known to have early\u2010onset MPSI (Hurler's syndrome). Bivariate analyses of the standardized natural logarithms of IDUA and HS levels were employed to develop the tool.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Every case of early\u2010onset MPSI was predicted correctly by the tool. No normal newborn was incorrectly identified as having early\u2010onset MPSI, whereas 12 normal newborns were so incorrectly identified by the Gifu NBS protocol. The PPV was estimated to be 99.9%.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Bivariate analysis of IDUA with HS in newborn DBS can accurately predict early MPSI symptoms, control false positive rates, and enhance presymptomatic treatment. This bivariate analysis\u2010based approach, which was developed for Krabbe disease, can be extended to additional screened disorders.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jmd2.12093","type":"journal-article","created":{"date-parts":[[2020,2,10]],"date-time":"2020-02-10T21:07:55Z","timestamp":1581368875000},"page":"35-42","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Development of a newborn screening tool for mucopolysaccharidosis type I based on bivariate normal limits: Using glycosaminoglycan and alpha\u2010L\u2010iduronidase determinations on dried blood spots to predict symptoms"],"prefix":"10.1002","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8187-8728","authenticated-orcid":false,"given":"Thomas J.","family":"Langan","sequence":"first","affiliation":[{"name":"Department of Neurology, School of Medicine and Biomedical Sciences University at Buffalo  Buffalo New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kabir","family":"Jalal","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Population Health Observatory, School of Public Health and Health Professions University at Buffalo  Buffalo New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3019-8970","authenticated-orcid":false,"given":"Amy L.","family":"Barczykowski","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Population Health Observatory, School of Public Health and Health Professions University at Buffalo  Buffalo New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Randy L.","family":"Carter","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Population Health Observatory, School of Public Health and Health Professions University at Buffalo  Buffalo New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Molly","family":"Stapleton","sequence":"additional","affiliation":[{"name":"Skeletal Dysplasia Research Lab, Nemours\/Alfred I. DuPont Hospital for Children  Wilmington Delaware"},{"name":"Department of Biological Sciences University of Delaware  Newark Delaware"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenji","family":"Orii","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medicine Gifu University  Gifu Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiyuki","family":"Fukao","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medicine Gifu University  Gifu Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hironori","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Shimane University  Shimane Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seiji","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Shimane University  Shimane Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shunji","family":"Tomatsu","sequence":"additional","affiliation":[{"name":"Skeletal Dysplasia Research Lab, Nemours\/Alfred I. DuPont Hospital for Children  Wilmington Delaware"},{"name":"Department of Biological Sciences University of Delaware  Newark Delaware"},{"name":"Department of Pediatrics, Graduate School of Medicine Gifu University  Gifu Japan"},{"name":"Department of Pediatrics Shimane University  Shimane Japan"},{"name":"Department of Pediatrics Thomas Jefferson University  Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,2,10]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320200308"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2018.01.003"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2013.06.007"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-016-9981-6"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200101183440304"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24246"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2013.11.015"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-019-01147-4"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2019.02.012"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijns3020006"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.113.6.1573"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23793"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-018-0371-3"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-018-0816-4"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-017-0098-3"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2017.194"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2017.06.048"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapediatrics.2018.0263"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-018-0129-y"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2005-0553"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2018.04.011"},{"volume-title":"Multivariate Statistics: A Practical Approach","year":"1988","author":"Johnson R","key":"e_1_2_11_23_1"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.1966.10480892"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.309.6947.102"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2016.11.285"},{"key":"e_1_2_11_27_1","unstructured":"Orphanet. The portal for rare diseases and orphan drugs. 2019. http:\/\/www.orpha.net. Accessed June 3 2019."},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/9780470316511"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2012.09.024"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e31820d5e67"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac5004135"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e3181fe5d9c"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-018-0101-x"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2016.35"},{"issue":"1","key":"e_1_2_11_35_1","first-page":"1","volume":"64","author":"Martin","year":"2015","journal-title":"Natl Vital Stat Rep"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-018-0130-5"}],"container-title":["JIMD Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmd2.12093","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jmd2.12093","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmd2.12093","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T18:46:44Z","timestamp":1693421204000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jmd2.12093"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,10]]},"references-count":35,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,3]]}},"alternative-id":["10.1002\/jmd2.12093"],"URL":"https:\/\/doi.org\/10.1002\/jmd2.12093","archive":["Portico"],"relation":{},"ISSN":["2192-8312","2192-8312"],"issn-type":[{"type":"print","value":"2192-8312"},{"type":"electronic","value":"2192-8312"}],"subject":[],"published":{"date-parts":[[2020,2,10]]},"assertion":[{"value":"2019-10-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-12-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-02-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}