{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T03:33:21Z","timestamp":1790134401235,"version":"4.0.1"},"reference-count":113,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Hypophosphatasia (HPP) is an inherited metabolic disease caused by loss-of-function mutations in the tissue non-specific alkaline phosphatase (TNAP) gene. Reduced activity of TNAP leads to the accumulation of its substrates, mainly inorganic pyrophosphate and pyridoxal-5\u2032-phosphate, metabolic aberrations that largely explain the musculoskeletal and systemic features of the disease. More than 400 ALPL mutations, mostly missense, are reported to date, transmitted by either autosomal dominant or recessive mode. Severe disease is rare, with incidence ranging from 1:100,000 to 1:300,000 live births, while the estimated prevalence of the less severe adult form is estimated to be between 1:3100 to 1:508, in different countries in Europe. Presentation largely varies, ranging from death in utero to asymptomatic adults. In infants and children, clinical features include skeletal, respiratory and neurologic complications, while recurrent, poorly healing fractures, muscle weakness and arthropathy are common in adults. Persistently low serum alkaline phosphatase is the cardinal biochemical feature of the disease. Management requires a dedicated multidisciplinary team. In mild cases, treatment is usually symptomatic. Severe cases, with life-threating or debilitating complications, can be successfully treated with enzyme replacement therapy with asfotase alfa.<\/jats:p>","DOI":"10.3390\/jcm10235676","type":"journal-article","created":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T05:02:36Z","timestamp":1638334956000},"page":"5676","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Hypophosphatasia"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8301-324X","authenticated-orcid":false,"given":"Symeon","family":"Tournis","sequence":"first","affiliation":[{"name":"Laboratory for the Research of Musculoskeletal System \u201cTh. Garofalidis\u201d, School of Medicine, National and Kapodistrian University of Athens, KAT General Hospital, 14561 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6501-3692","authenticated-orcid":false,"given":"Maria","family":"Yavropoulou","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, 1st Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens, School of Medicine, Laikon General Hospital, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9232-4042","authenticated-orcid":false,"given":"Stergios","family":"Polyzos","sequence":"additional","affiliation":[{"name":"First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Artemis","family":"Doulgeraki","sequence":"additional","affiliation":[{"name":"Department of Bone and Mineral Metabolism, Institute of Child Health, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/nrendo.2016.14","article-title":"Hypophosphatasia\u2014Aetiology, nosology, pathogenesis, diagnosis and treatment","volume":"12","author":"Whyte","year":"2016","journal-title":"Nat. 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