{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T13:56:21Z","timestamp":1787061381472,"version":"build-2736575974"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,12,28]],"date-time":"2024-12-28T00:00:00Z","timestamp":1735344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Health and Labor Sciences Research Grant for Research on Rare and Intractable Diseases from the Ministry of Health, Labor and Welfare, Japan","award":["JPMH23FC1033"],"award-info":[{"award-number":["JPMH23FC1033"]}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP22gk0110050h0003"],"award-info":[{"award-number":["JP22gk0110050h0003"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP23ek0109636s0301"],"award-info":[{"award-number":["JP23ek0109636s0301"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science, and Technology, Japan","doi-asserted-by":"crossref","award":["JP23K07294"],"award-info":[{"award-number":["JP23K07294"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science, and Technology, Japan","doi-asserted-by":"crossref","award":["JP23K07316"],"award-info":[{"award-number":["JP23K07316"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science, and Technology, Japan","doi-asserted-by":"crossref","award":["JP23K14954"],"award-info":[{"award-number":["JP23K14954"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Hypophosphatasia (HPP) is an inherited metabolic disease caused by deficiency of tissue nonspecific alkaline phosphatase (TNAP) caused by pathogenic variants of the ALPL gene (MIM 171760). The clinical manifestations of HPP vary, ranging from a lethal perinatal-onset type to a moderate late-onset type presenting with nonspecific symptoms, such as arthropathy and musculoskeletal pain. HPP is characterized by low TNAP activity and defective bone mineralization, leading to bone deformity and skeletal abnormalities. Moreover, this disease can cause systemic complications, such as muscle weakness, seizures, pain, and respiratory failure, leading to premature death in infants. This study aimed to evaluate whether measuring TNAP activity in dried blood spots (DBSs) can identify patients with HPP. We developed an assay to assess TNAP activity using DBSs and screened 45\u2009632 newborns born between February 2019 and March 2022 in Kumamoto Prefecture in Japan for HPP. We detected a single heterozygous variant of the ALPL gene in 5 newborns. During the clinical course follow-up, one newborn presented with HPP-related clinical manifestations. This is the first study on newborn screening (NBS) for HPP worldwide. NBS for HPP using DBSs may be practical and beneficial, as it is a high-throughput method. Moreover, the DBSs used for the TNAP assay are the same as those used for public-funded NBS worldwide. In the future, this system may be implemented as standard NBS for HPP.<\/jats:p>","DOI":"10.1093\/jbmrpl\/ziae172","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T23:25:53Z","timestamp":1734996353000},"source":"Crossref","is-referenced-by-count":5,"title":["Newborn screening for hypophosphatasia: development of a high-throughput tissue nonspecific alkaline phosphatase activity assay using dried blood spots"],"prefix":"10.1093","volume":"9","author":[{"given":"Yusuke","family":"Noda","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medical Sciences, Kumamoto University , Kumamoto ,","place":["Japan"]},{"name":"Department of Pediatrics, Kumamoto University Hospital , Kumamoto ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1328-6696","authenticated-orcid":false,"given":"Jun","family":"Kido","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kumamoto University Hospital , Kumamoto ,","place":["Japan"]},{"name":"Department of Pediatrics, Faculty of Life Sciences, Kumamoto University , Kumamoto 860-8556 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takaaki","family":"Sawada","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kumamoto University Hospital , Kumamoto ,","place":["Japan"]},{"name":"Department of Pediatrics, Faculty of Life Sciences, Kumamoto University , Kumamoto 860-8556 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kumamoto University Hospital , Kumamoto ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kousuke","family":"Kumeda","sequence":"additional","affiliation":[{"name":"KM Biologics Co., Ltd. , Kumamoto ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichiro","family":"Yoshida","sequence":"additional","affiliation":[{"name":"KM Biologics Co., Ltd. , Kumamoto ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keishin","family":"Sugawara","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Life Sciences, Kumamoto University , Kumamoto 860-8556 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimitoshi","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kumamoto University Hospital , Kumamoto ,","place":["Japan"]},{"name":"Department of Pediatrics, Faculty of Life Sciences, Kumamoto University , Kumamoto 860-8556 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,12,28]]},"reference":[{"issue":"1","key":"2025022505584765900_ref1","doi-asserted-by":"publisher","first-page":"4048","DOI":"10.1038\/s41467-023-39833-3","article-title":"The structural pathology for hypophosphatasia is caused by malfunctional tissue non-specific alkaline phosphatase","volume":"14","author":"Yu","year":"2023","journal-title":"Nat Commun"},{"key":"2025022505584765900_ref2","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.bone.2017.02.011","article-title":"Hypophosphatasia: an overview for 2017","volume":"102","author":"Whyte","year":"2017","journal-title":"Bone"},{"issue":"1","key":"2025022505584765900_ref3","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1297\/cpe.29.9","article-title":"Clinical practice guidelines for hypophosphatasis","volume":"29","author":"Michigami","year":"2020","journal-title":"Clin Pediatr Endocrinol"},{"key":"2025022505584765900_ref4","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1016\/j.jpeds.2019.01.049","article-title":"Natural history of perinatal and infantile hypophosphatasia: a retrospective study","volume":"209","author":"Whyte","year":"2019","journal-title":"J Pediatr"},{"issue":"2","key":"2025022505584765900_ref5","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1038\/s41431-020-00732-6","article-title":"Hypophosphatasia: a genetic-based nosology and new insights in genotype-phenotype correlation","volume":"29","author":"Mornet","year":"2021","journal-title":"Eur J Hum Genet"},{"issue":"2","key":"2025022505584765900_ref6","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1038\/jhg.2010.161","article-title":"Prevalence of c.1559delT in ALPL. 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