{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:17:12Z","timestamp":1784557032345,"version":"3.55.0"},"reference-count":10,"publisher":"Bioscientifica","issue":"1","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["edm.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,1,1]]},"abstract":"<jats:sec>\n                    <jats:title>Summary<\/jats:title>\n                    <jats:p>\n                      Hypophosphatasia (HPP) is a genetic disorder due to pathological variants in\n                      <jats:italic>ALPL<\/jats:italic>\n                      , the gene encoding tissue-nonspecific alkaline phosphatase (ALP). HPP is typically associated with bone-related symptoms, such as bone deformity, fractures and bone pain in children, but can appear in adults with symptoms resembling arthritis. A 22-year-old male experienced repeated and severe sudden attacks of joint pain in the elbows and knees. Magnetic resonance imaging and joint ultrasonography showed joint effusions indicating chronic inflammation. Blood biochemical tests revealed a remarkably low serum ALP level, and repeated examination confirmed a sustained low ALP level; urine phosphoethanolamine, plasma inorganic pyrophosphate and plasma pyridoxal-5\u2032-phosphate levels were elevated, raising concern for HPP. While the patient had no history of premature loss of primary teeth, fragility fractures, muscle weakness or abnormalities in growth, genetic testing revealed a likely pathogenic and a pathogenic heterozygous variant in the\n                      <jats:italic>ALPL<\/jats:italic>\n                      gene, i.e., c.979T&gt;C (p.Phe327Leu) and c.1559del (p.Leu520Argfs), confirming HPP. Additional genetic testing of his parents showed a heterozygous c.1559del variant in his father and a heterozygous c.979T&gt;C variant in his mother. A diagnosis of adult HPP due to compound heterozygous mutations was therefore confirmed. Enzyme replacement therapy with asfotase alfa was then introduced; no attacks of arthralgia occurred in the 1-year period since then. This case highlights the possibility of HPP in adults who present clinically with repeated joint symptoms and low serum ALP levels but without bone-related symptoms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Learning points<\/jats:title>\n                    <jats:list list-type=\"bullet\">\n                      <jats:list-item>\n                        <jats:p>A diagnosis of adult HPP without bone-related symptoms can be challenging.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>A reduction in tissue-nonspecific ALP activity leads to an accumulation of pyrophosphate in the joints, which can cause arthralgia.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>Some cases of adult HPP have arthralgia as the only presenting symptom.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>At one-year follow-up, enzyme replacement therapy with asfotase alfa might lead to a reduction in arthralgia attacks due to HPP.<\/jats:p>\n                      <\/jats:list-item>\n                    <\/jats:list>\n                  <\/jats:sec>","DOI":"10.1530\/edm-24-0121","type":"journal-article","created":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T06:43:29Z","timestamp":1737960209000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-2","source":"Crossref","is-referenced-by-count":0,"title":["Adult hypophosphatasia presenting with recurrent acute joint pain"],"prefix":"10.1530","volume":"2025","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0155-9177","authenticated-orcid":true,"given":"Hayao","family":"Yoshida","sequence":"first","affiliation":[{"name":"Department of Diabetes and Endocrinology, Shiga General Hospital, Moriyama, Japan"},{"name":"Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3844-1138","authenticated-orcid":true,"given":"Takaaki","family":"Murakami","sequence":"additional","affiliation":[{"name":"Department of Diabetes and Endocrinology, Shiga General Hospital, Moriyama, Japan"},{"name":"Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsubumi","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Sunouchi","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Endocrinology, The University of Tokyo Hospital, Tokyo, Japan"},{"name":"Osteoporosis Center, The University of Tokyo Hospital, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoko","family":"Hidaka","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Endocrinology, The University of Tokyo Hospital, Tokyo, Japan"},{"name":"Osteoporosis Center, The University of Tokyo Hospital, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuaki","family":"Ito","sequence":"additional","affiliation":[{"name":"Osteoporosis Center, The University of Tokyo Hospital, Tokyo, Japan"},{"name":"Division of Therapeutic Development for Intractable Bone Diseases, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromi","family":"Murakami","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidenori","family":"Kawasaki","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Akiyama","sequence":"additional","affiliation":[{"name":"Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsumi","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Department of Diabetes and Endocrinology, Shiga General Hospital, Moriyama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Yabe","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taizo","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Diabetes and Endocrinology, Shiga General Hospital, Moriyama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Best Pract Res Clin Rheumatol","first-page":"113","article-title":"Hypophosphatasia","volume":"22","author":"Mornet E","year":"2008","unstructured":"Mornet E\n\n. 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(https:\/\/doi.org\/10.1007\/s00198-021-06145-5)"}],"container-title":["Endocrinology, Diabetes &amp; Metabolism Case Reports"],"original-title":[],"link":[{"URL":"https:\/\/edm.bioscientifica.com\/view\/journals\/edm\/2025\/1\/EDM-24-0121.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/edm.bioscientifica.com\/downloadpdf\/journals\/edm\/2025\/1\/EDM-24-0121.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/edm.bioscientifica.com\/downloadpdf\/journals\/edm\/2025\/1\/EDM-24-0121.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:48:31Z","timestamp":1784555311000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/edm\/article\/3768"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,1]]},"references-count":10,"journal-issue":{"issue":"1"},"URL":"https:\/\/doi.org\/10.1530\/edm-24-0121","relation":{},"ISSN":["2052-0573"],"issn-type":[{"value":"2052-0573","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,1]]}}}