{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T10:22:32Z","timestamp":1794392552250,"version":"4.9.0"},"reference-count":28,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"vor","delay-in-days":309,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatrics International"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Serum alkaline phosphatase (ALP), a biomarker of bone and liver metabolism, is often elevated in children; however, the lower reference limit is rarely considered. Hypophosphatasia (HPP) is characterized by low ALP levels and impaired mineralization of bone and teeth. Although enzyme replacement therapy is available, mild forms are diagnosed late owing to subtle symptoms and ALP levels falling within the adult reference range. In Japan, ALP analysis methods were updated in 2020 and now require value conversion. Pediatricians unfamiliar with these standards may overlook low ALP levels. We investigated whether the disease distribution varies by age and identified key features critical for diagnosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed serum ALP levels of patients aged &lt;18\u2009years who visited three Nippon Medical School hospitals between January 2020 and December 2022. The inclusion criteria were ALP levels within the adult reference range but below age\u2010 and sex\u2010specific pediatric norms. Patient age, sex, and medical history were recorded.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 16,125 ALP measurements from 5513 individuals, 239 cases (132 males and 107 females) met the inclusion criteria. In neonates, preterm birth or low birth weight was common, and 55.6% of the infants had infections. School\u2010age children frequently present with a history of corticosteroid use, while adolescents often exhibit signs of malnutrition or chronic diarrhea. One patient had a prior HPP diagnosis, and two were newly diagnosed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings underscore the importance of recognizing low ALP levels in pediatric patients and maintaining a high index of suspicion for HPP and other treatable conditions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ped.70260","type":"journal-article","created":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T12:22:43Z","timestamp":1762431763000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Clinical features of low serum alkaline phosphatase levels in children: A retrospective study"],"prefix":"10.1111","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-6033-5872","authenticated-orcid":false,"given":"Mami","family":"Kurihara","sequence":"first","affiliation":[{"name":"Department of Pediatrics Nippon Medical School Musashikosugi Hospital  Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1762-9505","authenticated-orcid":false,"given":"Hanako","family":"Tajima","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Nippon Medical School Musashikosugi Hospital  Kanagawa Japan"},{"name":"Department of Pediatrics Nippon Medical School Hospital  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryu","family":"Ishii","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Nippon Medical School Tamanagayama Hospital  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Nippon Medical School Tamanagayama Hospital  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Migita","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Nippon Medical School Musashikosugi Hospital  Kanagawa 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