{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T07:25:58Z","timestamp":1763018758114,"version":"3.40.1"},"reference-count":10,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T00:00:00Z","timestamp":1742428800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T00:00:00Z","timestamp":1742428800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ital J Pediatr"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Hypophosphatasia (HPP) is a rare inherited disorder characterized by a deficiency of tissue-non-specific alkaline phosphatase (TNSALP) due to loss-of-function variants of the <jats:italic>ALPL<\/jats:italic> gene. HPP is characterized by an extremely variable age of onset and clinical presentation, largely depending on the type of genetic disruption. Childhood HPP commonly presents with skeletal deformities, bone fragility, precocious tooth loss, muscle weakness and sometimes neurological implications. Laboratory tests usually document low levels of alkaline phosphatase (ALP), and radiologic investigations show peculiar bone abnormalities. Treatment with human recombinant TNSALP (asfotase alpha, Strensiq<jats:sup>\u00ae<\/jats:sup>), available since 2015, is associated with a sudden improvement and a good safety profile.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Case presentation<\/jats:title>\n            <jats:p>A previously healthy 15-month-old girl presented with progressive \u201cgenu valgus\u201d and sudden limping. The patient was diagnosed with childhood HPP due to the presence of two <jats:italic>ALPL<\/jats:italic> variants, never described in compound heterozygosity: a missense variant c.571G\u2009&gt;\u2009A, p.(Glu191Lys), and a frameshift deletion c.963delG; p.(Lys322Argfs*44), both classified as pathogenetic. The child was promptly treated with asfotase alpha, and good improvement was quickly obtained. Efficacy, safety, and good tolerance persisted after a long-term follow-up of 6 years.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Pediatricians should consider HPP in children presenting with a suggestive clinical phenotype. Calcium-phosphorus metabolism, ALP, and vitamin B6 should always be investigated in suspected cases. Moreover, asfotase alfa represents a safe, well-tolerated, and effective drug in children with HPP.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s13052-025-01883-2","type":"journal-article","created":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T23:04:43Z","timestamp":1742511883000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Safety and efficacy of long term asfotase alfa treatment in childhood hypophosphatasia"],"prefix":"10.1186","volume":"51","author":[{"given":"Debora Mariarita","family":"d\u2019Angelo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federico","family":"Lauriola","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luisa","family":"Silvestrini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luigia","family":"Cinque","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Castori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulia","family":"Di Donato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Armando","family":"Di Ludovico","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saverio","family":"La Bella","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Chiarelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2904-2744","authenticated-orcid":false,"given":"Cosimo","family":"Giannini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luciana","family":"Breda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,3,20]]},"reference":[{"key":"1883_CR1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00198-023-06843-2","volume":"35","author":"E Rush","year":"2024","unstructured":"Rush E, Brandi ML, Khan A, Ali DS, Al-Alwani H, Almonaei K, et al. Proposed diagnostic criteria for the diagnosis of hypophosphatasia in children and adolescents: results from the HPP International Working Group. Osteoporos Int. 2024;35:1\u201310.","journal-title":"Osteoporos Int"},{"key":"1883_CR2","doi-asserted-by":"crossref","first-page":"1320516","DOI":"10.3389\/fendo.2023.1320516","volume":"14","author":"L Mart\u00ednez-Heredia","year":"2023","unstructured":"Mart\u00ednez-Heredia L, Mu\u00f1oz-Torres M, Sanabria-de la Torre R, Jim\u00e9nez-Ortas \u00c1, And\u00fajar-Vera F, Gonz\u00e1lez-Cejudo T, et al. Systemic effects of hypophosphatasia characterization of two novel variants in the ALPL gene. Front Endocrinol (Lausanne). 2023;14:1320516.","journal-title":"Front Endocrinol (Lausanne)"},{"key":"1883_CR3","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/nrendo.2016.14","volume":"12","author":"MP Whyte","year":"2016","unstructured":"Whyte MP. Hypophosphatasia - aetiology, nosology, pathogenesis, diagnosis and treatment. Nat Rev Endocrinol. 2016;12:233\u201346.","journal-title":"Nat Rev Endocrinol"},{"key":"1883_CR4","doi-asserted-by":"crossref","unstructured":"Baroncelli GI, Carlucci G, Freri E, Giuca MR, Guarnieri V, Navarra G et al. The diagnosis of hypophosphatasia in children as a multidisciplinary effort: an expert opinion. J Endocrinol Invest. 2023.","DOI":"10.1007\/s40618-023-02199-w"},{"key":"1883_CR5","doi-asserted-by":"crossref","unstructured":"Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17:405\u201324. https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1098360021030318","DOI":"10.1038\/gim.2015.30"},{"key":"1883_CR6","doi-asserted-by":"publisher","unstructured":"Mornet E, Yvard A, Taillandier A, Fauvert D, Simon-Bouy B. A molecular\u2010based estimation of the prevalence of hypophosphatasia in the European population. Ann Hum Genet. 2011;75:439\u201345. https:\/\/onlinelibrary.wiley.com\/doi\/https:\/\/doi.org\/10.1111\/j.1469-1809.2011.00642.x","DOI":"10.1111\/j.1469-1809.2011.00642.x"},{"key":"1883_CR7","doi-asserted-by":"publisher","unstructured":"Mannes I, Rothenbuhler A, Merzoug V, Di Rocco F, Linglart A, Adamsbaum C. Imaging patterns in pediatric hypophosphatasia. Pediatr Radiol. 2022;52:998\u20131006. https:\/\/doi.org\/10.1007\/s00247-021-05232-3.","DOI":"10.1007\/s00247-021-05232-3"},{"key":"1883_CR8","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1002\/humu.9159","volume":"22","author":"M Spentchian","year":"2003","unstructured":"Spentchian M, Merrien Y, Herasse M, Dobbie Z, Gl\u00e4ser D, Holder SE, et al. Severe hypophosphatasia: characterization of fifteen novel mutations in the ALPL gene. 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Bone. 2022;154:116204.","journal-title":"Bone"}],"container-title":["Italian Journal of Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13052-025-01883-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13052-025-01883-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13052-025-01883-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T23:05:13Z","timestamp":1742511913000},"score":1,"resource":{"primary":{"URL":"https:\/\/ijponline.biomedcentral.com\/articles\/10.1186\/s13052-025-01883-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,20]]},"references-count":10,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["1883"],"URL":"https:\/\/doi.org\/10.1186\/s13052-025-01883-2","relation":{},"ISSN":["1824-7288"],"issn-type":[{"value":"1824-7288","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,20]]},"assertion":[{"value":"24 April 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 January 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 March 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Ethics approval was not required for the publication of this case. A written consent for publication was obtained by the parents of the child.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"86"}}