{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T13:30:55Z","timestamp":1787059855371,"version":"build-2736575974"},"reference-count":10,"publisher":"Bioscientifica","issue":"2","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"vor","delay-in-days":93,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,4,1]]},"abstract":"\n Summary<\/jats:title>\n Hypophosphatasia (HPP) is a rare inherited metabolic disorder characterized by deficient activity of serum alkaline phosphatase due to loss-of-function mutations in the ALPL gene. Diagnosis confirmation, management, and follow-up of HPP are challenging, and clinical guidance is scant due to the difficulty in gathering high-level evidence. Asfotase alfa is the first long-term enzyme replacement therapy indicated in patients with pediatric-onset HPP to treat the bone manifestations of the disease. In the absence of large clinical studies, sharing clinical observations is an important source of information and support for clinicians. This article presents three case studies. A woman affected by HPP with manifestations of the disease at pediatric age began asfotase alfa therapy at the age of 43 years, resulting in improvements in bone density and epilepsy management. A man diagnosed with HPP in childhood had a severely compromised quality of life. He experienced improvements in bone fragility, respiratory function, sleep quality, and physical function with asfotase alfa therapy. Finally, a woman with infantile-onset HPP, presenting with severe bone deformity, musculoskeletal pain, pseudofractures, and cardiovascular and neurological involvement, showed radiological and clinical improvements in bone health, reduced pain, and increased walking autonomy during asfotase alfa treatment.<\/jats:p>\n <\/jats:sec>\n \n Learning points<\/jats:title>\n <\/jats:sec>","DOI":"10.1530\/edm-25-0050","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T13:55:40Z","timestamp":1781531740000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-2","source":"Crossref","is-referenced-by-count":0,"title":["Experiences with the use of asfotase alfa in three patients with childhood-onset hypophosphatasia"],"prefix":"10.1530","volume":"2026","author":[{"given":"Francesca","family":"Pigliaru","sequence":"first","affiliation":[{"name":"Endocrinology Unit, Department of Medical Sciences and Public Health, University of Cagliari, Monserrato, Cagliari, Italy 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Noto","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), Universit\u00e0 degli Studi di Palermo, Palermo, Italy 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8741-0592","authenticated-orcid":true,"given":"Maria Luisa","family":"Brandi","sequence":"additional","affiliation":[{"name":"IRCCS European Institute of Oncology, Milan, Italy 3"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","published-online":{"date-parts":[[2026,6,15]]},"reference":[{"key":"2026081809164107200_bib1","doi-asserted-by":"crossref","first-page":"2735","DOI":"10.1210\/jc.2018-02335","article-title":"Efficacy and safety of asfotase alfa in infants and young children with hypophosphatasia: a phase 2 open-label study","volume":"104","author":"Hofmann","year":"2019","journal-title":"J Clin Endocrinol Metab"},{"key":"2026081809164107200_bib2","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1007\/s00198-023-06844-1","article-title":"Hypophosphatasia diagnosis: current state of the art and proposed diagnostic criteria for children and adults","volume":"35","author":"Khan","year":"2024","journal-title":"Osteoporos Int"},{"key":"2026081809164107200_bib3","doi-asserted-by":"crossref","DOI":"10.1016\/j.bone.2024.117219","article-title":"Efficacy and safety of asfotase alfa in patients with hypophosphatasia: a systematic review","volume":"188","author":"Shirinezhad","year":"2024","journal-title":"Bone"},{"key":"2026081809164107200_bib4","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1016\/j.bone.2007.01.020","article-title":"Pyridoxine-responsive seizures as the first symptom of infantile hypophosphatasia caused by two novel missense mutations (c.677T>C, p.M226T; 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