{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T03:14:15Z","timestamp":1791429255923,"version":"4.3.3"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T00:00:00Z","timestamp":1742169600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006396","name":"Alexion","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006396","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Hypophosphatasia (HPP) is an inherited disorder that affects bone and tooth mineralization, among other body systems. HPP is caused by pathogenic variants in the alkaline phosphatase-liver (ALPL) gene, which encodes tissue nonspecific alkaline phosphatase. One major challenge in diagnosing HPP is interpreting variant of uncertain significance (VUS), which can create uncertainty for patients and healthcare professionals, leading to delays in diagnosis and treatment or incorrect diagnoses. Since February 2021, the ALPLgene variant consortium has reclassified 100 VUS using adjusted American College of Medical Genetics\/Association for Molecular Pathology criteria. Of these, 11 were reclassified as pathogenic, 62 as likely pathogenic, three as likely benign, one as benign, and 23 remained as VUS; out of 100 variants, there were 81 missense, eight frameshifts, four in-frame deletions, two intronic, two synonymous, two nonsense, and one splice site variant. In vitrofunctional testing of the variant\u2019s residual enzymatic activity and its dominant negative effect (DNE) was required for 40 variants.Out of 40 variants tested, 72% showed &amp;lt;30% residual activity and were reclassified as pathogenic or likely pathogenic. Among these, 48% exhibited a DNE. All variants with \u02c215% residual activity showed a DNE, while those with over 20% did not. In terms of domains, all tested variants in the active site domain and 75% of those in the homodimeric interface showed &amp;lt;30% residual activity. The consortium\u2019s reclassification of 100 ALPLvariants has resulted in a 21% increase in the number of variants in the Johannes Kepler University ALPLgene variant database. Furthermore, 136 new genotypes with 118 associated phenotypes, including asymptomatic states, have been added. These expanded resources will help improve genetic counseling for patients and families affected by ALPLvariants and enable faster diagnosis and medical decision-making.<\/jats:p>","DOI":"10.1093\/jbmrpl\/ziaf044","type":"journal-article","created":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T08:48:16Z","timestamp":1742201296000},"source":"Crossref","is-referenced-by-count":9,"title":["The ALPL gene variant project: results of the first 100 reclassified variants"],"prefix":"10.1093","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4419-8421","authenticated-orcid":false,"given":"Mariam R","family":"Farman","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, Johannes Kepler University Linz , Krankenhausstrasse 26-30, 4020 Linz ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4244-7954","authenticated-orcid":false,"given":"Theodora","family":"Malli","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Genetic Diagnostics, Ordensklinikum Linz , Seilerst\u00e4tte 4, 4010 Linz ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4924-9010","authenticated-orcid":false,"given":"Catherine","family":"Rehder","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center , Durham NC 27705 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5654-6190","authenticated-orcid":false,"given":"Gerald","family":"Webersinke","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Genetic Diagnostics, Ordensklinikum Linz , Seilerst\u00e4tte 4, 4010 Linz ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4741-8442","authenticated-orcid":false,"given":"Cheryl","family":"Rockman-Greenberg","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Child Health, Rady Faculty of Health Sciences, University of Manitoba , Winnipeg R3a 1s1 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9980-9138","authenticated-orcid":false,"given":"Kathryn","family":"Dahir","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center, Program for Metabolic Bone Disorders , Nashville, TN 37232 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5524-2646","authenticated-orcid":false,"given":"Gabriel \u00c1","family":"Martos-Moreno","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics & Pediatric Endocrinology, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, IIS La Princesa , 28009 Madrid ,","place":["Spain"]},{"name":"Department of Pediatrics, Universidad Aut\u00f3noma de Madrid , 28029 Madrid ,","place":["Spain"]},{"name":"CIBER Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n. ISCIII , 28029 Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3455-002X","authenticated-orcid":false,"given":"Agn\u00e8s","family":"Linglart","sequence":"additional","affiliation":[{"name":"Paris Saclay University, INSERM, AP-HP, Bic\u00eatre Paris-Saclay Hospital , 94270 Le Kremlin-Bic\u00eatre ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6517-8825","authenticated-orcid":false,"given":"Keiichi","family":"Ozono","sequence":"additional","affiliation":[{"name":"ISEIKAI International General Hospital , 530-0052 Osaka ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1154-3388","authenticated-orcid":false,"given":"Lothar","family":"Seefried","sequence":"additional","affiliation":[{"name":"Julius-Maximilian University , 97074 W\u00fcrzburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0104-1563","authenticated-orcid":false,"given":"Guillermo","family":"del Angel","sequence":"additional","affiliation":[{"name":"Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca , Boston, MA 02210 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4288-8534","authenticated-orcid":false,"given":"Francesca","family":"Barbazza","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, Johannes Kepler University Linz , Krankenhausstrasse 26-30, 4020 Linz ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5435-9155","authenticated-orcid":false,"given":"Sara","family":"Shojaei","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, Johannes Kepler University Linz , Krankenhausstrasse 26-30, 4020 Linz ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4606-6051","authenticated-orcid":false,"given":"Jessica","family":"Ebner-Jahn","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, Johannes Kepler University Linz , Krankenhausstrasse 26-30, 4020 Linz ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4752-5457","authenticated-orcid":false,"given":"Florian","family":"H\u00f6gler","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, Johannes Kepler University Linz , Krankenhausstrasse 26-30, 4020 Linz ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9468-4893","authenticated-orcid":false,"given":"Erica B","family":"Nading","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center , Durham NC 27705 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7594-4511","authenticated-orcid":false,"given":"Erin","family":"Huggins","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center , Durham NC 27705 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8147-7315","authenticated-orcid":false,"given":"Eric T","family":"Rush","sequence":"additional","affiliation":[{"name":"Division of Clinical Genetics, Children's Mercy Hospital Kansas City , Kansas City, MO 64108 ,","place":["United States"]},{"name":"Department of Internal Medicine, University of Kansas School of Medicine , Kansas City, KS 66103 ,","place":["United States"]},{"name":"Department of Pediatrics, University of Missouri \u2013 Kansas City School of Medicine , Kansas City, MO 64108 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2859-7246","authenticated-orcid":false,"given":"Ahmed","family":"El-Gazzar","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, Johannes Kepler University Linz , Krankenhausstrasse 26-30, 4020 Linz ,","place":["Austria"]},{"name":"Division of Pulmonology, Department of Internal Medicine II, Medical University of Vienna, Comprehensive Cancer Center Vienna , 1090 Vienna,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6079-4653","authenticated-orcid":false,"given":"Josephine T","family":"Tauer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, Johannes Kepler University Linz , Krankenhausstrasse 26-30, 4020 Linz ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8251-909X","authenticated-orcid":false,"given":"Priya S","family":"Kishnani","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center , Durham NC 27705 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4328-6304","authenticated-orcid":false,"given":"Wolfgang","family":"H\u00f6gler","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, Johannes Kepler University Linz , Krankenhausstrasse 26-30, 4020 Linz ,","place":["Austria"]},{"name":"Department of Pediatrics and Adolescent Medicine, Centre for Growth and Osteology, Kepler University Hospital Linz , 4020 Linz ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,3,17]]},"reference":[{"issue":"1","key":"2025052712445197400_ref1","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1042\/cs0970073","article-title":"Hypophosphatasia: diagnostic application of linked DNA markers in the dominantly inherited adult form","volume":"97","author":"Iqbal","year":"1999","journal-title":"Clin Sci (Lond)"},{"issue":"24","key":"2025052712445197400_ref2","doi-asserted-by":"publisher","first-page":"12002","DOI":"10.1016\/S0021-9258(18)37885-2","article-title":"Structure of the human liver\/bone\/kidney alkaline phosphatase gene","volume":"263","author":"Weiss","year":"1988","journal-title":"J Biol Chem"},{"issue":"2","key":"2025052712445197400_ref3","first-page":"286","article-title":"Infantile hypophosphatasia: localization within chromosome region 1p36.1-34 and prenatal diagnosis using linked DNA markers","volume":"46","author":"Greenberg","year":"1990","journal-title":"Am J Hum Genet"},{"issue":"1","key":"2025052712445197400_ref4","doi-asserted-by":"publisher","first-page":"4048","DOI":"10.1038\/s41467-023-39833-3","article-title":"The structural pathology for hypophosphatasia caused by malfunctional tissue non-specific alkaline phosphatase","volume":"14","author":"Yu","year":"2023","journal-title":"Nat Commun"},{"issue":"1","key":"2025052712445197400_ref5","doi-asserted-by":"publisher","first-page":"13","DOI":"10.33176\/AACB-19-00031","article-title":"Hypophosphatasia: biological and clinical aspects, avenues for therapy","volume":"41","author":"Salles","year":"2020","journal-title":"Clin Biochem Rev"},{"issue":"5","key":"2025052712445197400_ref6","doi-asserted-by":"publisher","DOI":"10.20945\/2359-3997000000626","article-title":"Hypophosphatasia: from birth to adulthood","volume":"67","author":"Reis","year":"2023","journal-title":"Arch Endocrinol Metab"},{"issue":"4","key":"2025052712445197400_ref7","doi-asserted-by":"publisher","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 Rev Endocrinol"},{"key":"2025052712445197400_ref8","doi-asserted-by":"publisher","DOI":"10.1530\/EC-22-0240","article-title":"Growth and disease burden in children with hypophosphatasia","volume":"12","author":"H\u00f6gler","year":"2023","journal-title":"Endocr Connect"},{"issue":"11","key":"2025052712445197400_ref9","doi-asserted-by":"publisher","first-page":"2171","DOI":"10.1002\/jbmr.4130","article-title":"Burden of illness in adults with hypophosphatasia: data from the global hypophosphatasia patient registry","volume":"35","author":"Seefried","year":"2020","journal-title":"J Bone Miner Res"},{"issue":"356","key":"2025052712445197400_ref10","first-page":"e1","article-title":"Hypophosphatasia: clinical manifestations, diagnostic recommendations and therapeutic options","volume":"88","author":"Martos-Moreno","year":"2018","journal-title":"Anales de Pediatr\u00eda (English Edition)"},{"issue":"1","key":"2025052712445197400_ref11","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/1750-1172-2-40","article-title":"Hypophosphatasia","volume":"2","author":"Mornet","year":"2007","journal-title":"Orphanet J Rare Dis"},{"key":"2025052712445197400_ref12","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/j.bone.2015.02.022","article-title":"Hypophosphatasia: validation and expansion of the clinical nosology for children from 25years experience with 173 pediatric patients","volume":"75","author":"Whyte","year":"2015","journal-title":"Bone"},{"issue":"1","key":"2025052712445197400_ref13","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1186\/s12891-019-2420-8","article-title":"Diagnostic delay is common among patients with hypophosphatasia: initial findings from a longitudinal, prospective, global registry","volume":"20","author":"H\u00f6gler","year":"2019","journal-title":"BMC Musculoskelet Disord"},{"issue":"5","key":"2025052712445197400_ref14","doi-asserted-by":"publisher","first-page":"5S51-5S56","DOI":"10.1016\/S0929-693X(18)30014-9","article-title":"Genetics of hypophosphatasia","volume":"24","author":"Mornet","year":"2017","journal-title":"Arch Pediatr"},{"issue":"6","key":"2025052712445197400_ref15","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1136\/archdischild-2015-309579","article-title":"Transformative therapy in hypophosphatasia","volume":"101","author":"Bishop","year":"2016","journal-title":"Arch Dis Child"},{"key":"2025052712445197400_ref16","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.jpeds.2016.01.045","article-title":"A diagnostic algorithm for children with low alkaline phosphatase activities: lessons learned from laboratory screening for Hypophosphatasia","volume":"172","author":"Saraff","year":"2016","journal-title":"J Pediatr"},{"key":"2025052712445197400_ref17","doi-asserted-by":"publisher","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"},{"issue":"3","key":"2025052712445197400_ref18","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1007\/s00198-023-06859-8","article-title":"The challenge of hypophosphatasia diagnosis in adults: results from the HPP international working group literature surveillance","volume":"35","author":"Brandi","year":"2024","journal-title":"Osteoporos Int"},{"key":"2025052712445197400_ref19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1159\/000540692","article-title":"Challenges in hypophosphatasia: suspicion, diagnosis, genetics, management, and follow-up","volume":"1\u201310","author":"Montero-Lopez","year":"2024","journal-title":"Horm Res Paediatr"},{"issue":"6","key":"2025052712445197400_ref20","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1111\/cen.15063","article-title":"Enzyme replacement therapy for hypophosphatasia\u2014the current paradigm","volume":"101","author":"Schindeler","year":"2024","journal-title":"Clin Endocrinol"},{"issue":"3","key":"2025052712445197400_ref21","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1007\/s00223-022-01039-y","article-title":"Diagnostic approach to patients with low serum alkaline phosphatase","volume":"112","author":"Riancho","year":"2023","journal-title":"Calcif Tissue Int"},{"issue":"3","key":"2025052712445197400_ref22","doi-asserted-by":"publisher","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"},{"issue":"5","key":"2025052712445197400_ref23","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"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","volume":"17","author":"Richards","year":"2015","journal-title":"Genetics in Medicine"},{"key":"2025052712445197400_ref24","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2020.577152","article-title":"Mastermind: a comprehensive genomic association search engine for empirical evidence curation and genetic variant interpretation","volume":"11","author":"Chunn","year":"2020","journal-title":"Front Genet"},{"key":"2025052712445197400_ref25","volume-title":"The PyMOL Molecular Graphics System","author":"DeLano","year":"2002"},{"issue":"1","key":"2025052712445197400_ref26","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The protein data Bank","volume":"28","author":"Berman","year":"2000","journal-title":"Nucleic Acids Res"},{"issue":"35","key":"2025052712445197400_ref27","doi-asserted-by":"publisher","first-page":"24168","DOI":"10.1074\/jbc.M114.576843","article-title":"Molecular evolution of the tissue-nonspecific alkaline phosphatase allows prediction and validation of missense mutations responsible for Hypophosphatasia","volume":"289","author":"Silvent","year":"2014","journal-title":"J Biol Chem"},{"issue":"D1","key":"2025052712445197400_ref28","doi-asserted-by":"publisher","first-page":"D862","DOI":"10.1093\/nar\/gkv1222","article-title":"ClinVar: public archive of interpretations of clinically relevant variants","volume":"44","author":"Landrum","year":"2016","journal-title":"Nucleic Acids Res"},{"issue":"7","key":"2025052712445197400_ref29","doi-asserted-by":"publisher","first-page":"1250","DOI":"10.1002\/humu.24010","article-title":"Large-scale in vitrofunctional testing and novel variant scoring via protein modeling provide insights into alkaline phosphatase activity in hypophosphatasia","volume":"41","author":"Del Angel","year":"2020","journal-title":"Hum Mutat"},{"issue":"33","key":"2025052712445197400_ref30","doi-asserted-by":"publisher","first-page":"31171","DOI":"10.1074\/jbc.M102788200","article-title":"Structural evidence for a functional role of human tissue nonspecific alkaline phosphatase in bone mineralization","volume":"276","author":"Mornet","year":"2001","journal-title":"J Biol Chem"},{"issue":"6","key":"2025052712445197400_ref31","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1007\/s00774-017-0888-6","article-title":"Genetic analysis of adults heterozygous for ALPL mutations","volume":"36","author":"Taillandier","year":"2018","journal-title":"J Bone Miner Metab"},{"issue":"1","key":"2025052712445197400_ref32","doi-asserted-by":"publisher","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":"10","author":"Fauvert","year":"2009","journal-title":"BMC Med Genet"},{"key":"2025052712445197400_ref33","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1093\/hmg\/8.6.1039","article-title":"Correlations of genotype and phenotype in hypophosphatasia","volume":"8","author":"Zurutuza","year":"1999","journal-title":"Hum Mol Genet"},{"key":"2025052712445197400_ref34","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1007\/978-94-017-7197-9_2","article-title":"Molecular genetics of Hypophosphatasia and phenotype-genotype correlations","volume-title":"Subcell Biochem","author":"Mornet","year":"2015"},{"issue":"1","key":"2025052712445197400_ref35","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1007\/s004390100546","article-title":"A molecular approach to dominance in hypophosphatasia","volume":"109","author":"Lia-Baldini","year":"2001","journal-title":"Hum Genet"},{"issue":"1","key":"2025052712445197400_ref36","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1210\/jc.2015-3462","article-title":"Asfotase Alfa treatment improves survival for perinatal and infantile hypophosphatasia","volume":"101","author":"Whyte","year":"2016","journal-title":"The Journal of Clinical Endocrinology & Metabolism"},{"issue":"1","key":"2025052712445197400_ref37","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1297\/cpe.29.9","article-title":"Clinical practice guidelines for hypophosphatasia*","volume":"29","author":"Michigami","year":"2020","journal-title":"Clin Pediatr Endocrinol"},{"issue":"1","key":"2025052712445197400_ref38","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1186\/s13023-024-03048-6","article-title":"Effectiveness of asfotase alfa for treatment of adults with hypophosphatasia: results from a global registry","volume":"19","author":"Kishnani","year":"2024","journal-title":"Orphanet J Rare Dis"},{"key":"2025052712445197400_ref39","volume-title":"Study of ALXN1850 in Participants with Hypophosphatasia (HPP)","author":"Alexion Pharmaceuticals, Inc","year":"2023"}],"container-title":["JBMR Plus"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jbmrplus\/advance-article-pdf\/doi\/10.1093\/jbmrpl\/ziaf044\/62427280\/ziaf044.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmrplus\/article-pdf\/9\/6\/ziaf044\/62427280\/ziaf044.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmrplus\/article-pdf\/9\/6\/ziaf044\/62427280\/ziaf044.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T16:45:01Z","timestamp":1748364301000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmrplus\/article\/doi\/10.1093\/jbmrpl\/ziaf044\/8081574"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,17]]},"references-count":39,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,4,30]]}},"URL":"https:\/\/doi.org\/10.1093\/jbmrpl\/ziaf044","relation":{},"ISSN":["2473-4039"],"issn-type":[{"value":"2473-4039","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,6]]},"published":{"date-parts":[[2025,3,17]]},"article-number":"ziaf044"}}