{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T23:07:30Z","timestamp":1788995250633,"version":"build-2803163510"},"reference-count":18,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Adult-onset hypophosphatasia manifests after age 18, and is characterised by reduced tissue-nonspecific alkaline phosphatase activity. This can lead to fractures, pseudo-fractures, osteomalacia, decreased bone density (bone loss), muscle weakness, myalgia, arthralgia, headache, dental symptoms (loss of permanent teeth, periodontal disease), and pseudogout. Over 480 distinct genetic mutations have been identified to date, with eight cases reported for the c.572A\u2009&amp;gt;\u2009G (p.Glu191Gly) mutation. However, all reported cases involved compound heterozygous mutations, and there have been no previous reports of cases of a single heterozygous mutation. We report the case of a 40-year-old woman with persistent hypophosphatasia, elevated urinary phosphoethanolamine levels suggesting adult-onset hypophosphatasia, and a heterozygous missense mutation (c.572A\u2009&amp;gt;\u2009G p.Glu191Gly) in the ALPL gene according to genetic testing. Treatment with subcutaneous injections of aspartate phosphatase alpha was initiated, which was followed by significant improvement of the pain, enhanced range of motion in both upper limbs, and improved gait. This patient\u2019s case differed from previously reported cases in that it involved a heterozygous c.572A\u2009&amp;gt;\u2009G (p.Glu191Gly) mutation alone in adult-onset hypophosphatasia. Adult-onset hypophosphatasia is an extremely rare disorder. However, its symptoms resemble those of systemic rheumatic diseases such as polymyalgia rheumatica and fibromyalgia, and rheumatologists may encounter this condition in routine clinical practice. Importantly, it can be detected based on low serum ALP levels.<\/jats:p>","DOI":"10.1093\/mrcr\/rxag082","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T11:38:02Z","timestamp":1787657882000},"source":"Crossref","is-referenced-by-count":0,"title":["Adult hypophosphatasia with a single heterozygous c.572A\u2009&amp;gt;\u2009G p.Glu191Gly mutation in the\n                    <i>ALPL<\/i>\n                    gene: Case report"],"prefix":"10.1093","volume":"10","author":[{"given":"Kota","family":"Hyakuna","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Wakayama Medical University , Wakayama ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2076-1603","authenticated-orcid":false,"given":"Shigeru","family":"Iwata","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Wakayama Medical University , Wakayama ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taro","family":"Nishikawa","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Wakayama Medical University , Wakayama ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kodai","family":"Ueno","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Wakayama Medical University , Wakayama ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuta","family":"Shimomura","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Wakayama Medical University , Wakayama ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeru","family":"Sonoda","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Wakayama Medical University , Wakayama ,","place":["Japan"]},{"name":"Department of Respiratory Medicine, National Hospital Organization Wakayama Hospital , Wakayama ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Kato","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Wakayama Medical University , Wakayama ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Matsumiya","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Wakayama Medical University , Wakayama ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takao","family":"Fujii","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Wakayama Medical University , Wakayama ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"2026090918312209300_ref1","volume-title":"Clinical Practice Guidelines for Hypophosphatasia (in Japanese) [Internet]","author":"Hypophosphatasia Clinical Practice Guidelines Development Committee","year":"2019"},{"key":"2026090918312209300_ref2","doi-asserted-by":"crossref","first-page":"116947","DOI":"10.1016\/j.bone.2023.116947","article-title":"The global ALPL gene variant classification project: dedicated to deciphering variants","volume":"178","author":"Farman","year":"2024","journal-title":"Bone"},{"key":"2026090918312209300_ref3","doi-asserted-by":"crossref","first-page":"230","DOI":"10.11138\/ccmbm\/2017.14.1.230","article-title":"Hypophosphatasia: clinical manifestation and burden of disease in adult patients","volume":"14","author":"Conti","year":"2017","journal-title":"Clin Cases Miner Bone Metab"},{"key":"2026090918312209300_ref4","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1007\/s00223-025-01356-y","article-title":"Diagnosis and treatment of hypophosphatasia","volume":"116","author":"Seefried","year":"2025","journal-title":"Calcif Tissue Int"},{"key":"2026090918312209300_ref5","doi-asserted-by":"crossref","first-page":"dgaa324","DOI":"10.1210\/clinem\/dgaa324","article-title":"Mineral intake and clinical symptoms in adult patients with hypophosphatasia","volume":"105","author":"Kuehn","year":"2020","journal-title":"J Clin Endocrinol Metab"},{"key":"2026090918312209300_ref6","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s00223-019-00626-w","article-title":"Hypophosphatasia in Japan: ALPL mutation analysis in 98 unrelated patients","volume":"106","author":"Michigami","year":"2020","journal-title":"Calcif Tissue Int"},{"key":"2026090918312209300_ref7","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1210\/jcem.85.2.6373","article-title":"Asp361Val mutant of alkaline phosphatase found in patients with dominantly inherited hypophosphatasia inhibits the activity of the wild-type enzyme","volume":"85","author":"M\u00fcller","year":"2000","journal-title":"J Clin Endocrinol Metab"},{"key":"2026090918312209300_ref8","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/1471-2350-10-51","article-title":"Mild forms of hypophosphatasia mostly result from dominant negative effect of severe alleles or from compound heterozygosity for severe and moderate alleles","volume":"6","author":"Fauvert","year":"2009","journal-title":"BMC Med Genet"},{"key":"2026090918312209300_ref9","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1136\/jmg.40.8.605","article-title":"Molecular study of three cases of odontohypophosphatasia resulting from heterozygosity for mutations in the tissue 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