{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T16:37:12Z","timestamp":1789663032346,"version":"4.0.1"},"reference-count":36,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2018,5,1]],"date-time":"2018-05-01T00:00:00Z","timestamp":1525132800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"funder":[{"name":"Shriners Hospitals for Children, USA"},{"name":"Enobia Pharma, Montreal, Canada"},{"name":"Alexion Pharmaceuticals, Inc., New Haven, CT, USA"},{"name":"The Clark and Mildred Cox Inherited Metabolic Bone Disease Research Fund"},{"name":"The Hypophosphatasia Research Fund"}],"content-domain":{"domain":["clinicalkey.jp","clinicalkey.com","clinicalkey.es","clinicalkey.com.au","clinicalkey.fr","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bone"],"published-print":{"date-parts":[[2018,5]]},"DOI":"10.1016\/j.bone.2018.01.022","type":"journal-article","created":{"date-parts":[[2018,1,31]],"date-time":"2018-01-31T10:49:28Z","timestamp":1517395768000},"page":"96-106","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":53,"special_numbering":"C","title":["Hypophosphatasia: Biochemical hallmarks validate the expanded pediatric clinical nosology"],"prefix":"10.1016","volume":"110","author":[{"given":"Michael P.","family":"Whyte","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9568-5775","authenticated-orcid":false,"given":"Stephen P.","family":"Coburn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence M.","family":"Ryan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen L.","family":"Ericson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bone.2018.01.022_bb0005","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.bone.2017.02.011","article-title":"Hypophosphatasia: an overview for 2017","volume":"102","author":"Whyte","year":"2017","journal-title":"Bone"},{"key":"10.1016\/j.bone.2018.01.022_bb0010","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/nrendo.2016.14","article-title":"Hypophosphatasia: aetiology, nosology, pathogenesis, diagnosis and treatment","volume":"12","author":"Whyte","year":"2016","journal-title":"Nat. Rev. Endocrinol."},{"key":"10.1016\/j.bone.2018.01.022_bb0015","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1007\/s00223-015-0079-1","article-title":"Alkaline phosphatase and hypophosphatasia","volume":"98","author":"Millan","year":"2016","journal-title":"Calcif. Tissue Int."},{"key":"10.1016\/j.bone.2018.01.022_bb0020","series-title":"Genetics of Bone Biology and Skeletal Disease","first-page":"481","article-title":"Hypophosphatasia and how alkaline phosphatase promotes mineralization","author":"Whyte","year":"2018"},{"key":"10.1016\/j.bone.2018.01.022_bb0025","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/S0140-6736(65)91422-4","article-title":"Excretion of inorganic pyrophosphate in hypophosphatasia","volume":"2","author":"Russell","year":"1965","journal-title":"Lancet"},{"key":"10.1016\/j.bone.2018.01.022_bb0030","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1172\/JCI106589","article-title":"Inorganic pyrophosphate in plasma in normal persons and in patients with hypophosphatasia, osteogenesis imperfecta, and other disorders of bone","volume":"50","author":"Russell","year":"1971","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.bone.2018.01.022_bb0035","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1038\/212901a0","article-title":"Effect of pyrophosphate on hydroxyapatite and its implications in calcium homeostasis","volume":"212","author":"Fleisch","year":"1966","journal-title":"Nature"},{"key":"10.1016\/j.bone.2018.01.022_bb0040","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1172\/JCI112031","article-title":"Markedly increased circulating pyridoxal-5\u2032-phosphate levels in hypophosphatasia: alkaline phosphatase acts in vitamin B6 metabolism","volume":"76","author":"Whyte","year":"1985","journal-title":"J. Clin. Invest."},{"issue":"Suppl. II","key":"10.1016\/j.bone.2018.01.022_bb0045","first-page":"1","article-title":"Phosphorylethanolamine and hypophosphatasia","volume":"15","author":"Rasmussen","year":"1968","journal-title":"Dan. Med. Bull."},{"key":"10.1016\/j.bone.2018.01.022_bb0050","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1126\/science.3276003","article-title":"Structural and functional roles of glycosyl-phosphatidylinositol in membranes","volume":"239","author":"Low","year":"1988","journal-title":"Science"},{"key":"10.1016\/j.bone.2018.01.022_bb0055","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.bone.2015.02.022","article-title":"Hypophosphatasia: validation and expansion of the clinical nosology for children from 25 years experience with 173 pediatric patients","volume":"75","author":"Whyte","year":"2015","journal-title":"Bone"},{"key":"10.1016\/j.bone.2018.01.022_bb0060","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1056\/NEJMoa1106173","article-title":"Enzyme replacement therapy in life-threatening hypophosphatasia","volume":"366","author":"Whyte","year":"2012","journal-title":"New Engl J Med"},{"key":"10.1016\/j.bone.2018.01.022_bb0065","first-page":"1","article-title":"Asfotase alfa therapy for children with hypophosphatasia","volume":"1:e85971","author":"Whyte","year":"2016","journal-title":"JCI Insight"},{"key":"10.1016\/j.bone.2018.01.022_bb0070","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; c.1112C>T, p.T371I) of the tissue-nonspecific alkaline phosphatase gene","volume":"40","author":"Baumgartner-Sigl","year":"2007","journal-title":"Bone"},{"key":"10.1016\/j.bone.2018.01.022_bb0075","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1097\/00005792-197909000-00001","article-title":"Adult hypophosphatasia: clinical, laboratory and genetic investigation of a large kindred with review of the literature","volume":"58","author":"Whyte","year":"1979","journal-title":"Medicine (Baltimore)"},{"key":"10.1016\/j.bone.2018.01.022_bb0080","doi-asserted-by":"crossref","first-page":"676","DOI":"10.4158\/EP.12.6.676","article-title":"Low serum alkaline phosphatase activity with pathologic fracture: case report and brief review of adult hypophosphatasia","volume":"12","author":"Khandwala","year":"2006","journal-title":"Endocr. Pract."},{"key":"10.1016\/j.bone.2018.01.022_bb0085","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1002\/jbmr.2110","article-title":"Calcific periarthritis as the only clinical manifestation of hypophosphatasia in middle-aged sisters","volume":"29","author":"Gua\u00f1abens","year":"2014","journal-title":"J. Bone Miner. Res."},{"key":"10.1016\/j.bone.2018.01.022_bb0090","series-title":"Tissue Nonspecific Alkaline Phosphatase Gene Mutations Database Yvelines (France). SESEP Laboratory at the University of Versailles-Saint Quentin","author":"Mornet","year":"2017"},{"key":"10.1016\/j.bone.2018.01.022_bb0095","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1016\/0002-9343(57)90124-9","article-title":"Hypophosphatasia","volume":"22","author":"Fraser","year":"1957","journal-title":"Am. J. Med."},{"key":"10.1016\/j.bone.2018.01.022_bb0100","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1002\/jbmr.3075","article-title":"Hypophosphatasia: enzyme replacement therapy bring new opportunities and new challenges","volume":"32","author":"Whyte","year":"2017","journal-title":"J. Bone Miner. Res."},{"key":"10.1016\/j.bone.2018.01.022_bb0105","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/0002-9343(78)90189-4","article-title":"The urinary excretion of phosphoethanolamine in diseases other than hypophosphatasia","volume":"64","author":"Licata","year":"1978","journal-title":"Am. J. Med."},{"key":"10.1016\/j.bone.2018.01.022_bb0110","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.bone.2016.08.019","article-title":"Hypophosphatasia: natural history study of 101 affected children studied at a single research center","volume":"93","author":"Whyte","year":"2016","journal-title":"Bone"},{"key":"10.1016\/j.bone.2018.01.022_bb0115","doi-asserted-by":"crossref","DOI":"10.1002\/jbmr.3377","article-title":"Validation of a novel scoring system for changes in skeletal manifestations of hypophosphatasia in newborns, infants, and children: the radiographic global impression of change scale","author":"Whyte","year":"2018","journal-title":"J Bone Miner Res"},{"key":"10.1016\/j.bone.2018.01.022_bb0120","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1002\/jbmr.5650070602","article-title":"X-linked hypophosphatemic rickets: a study (with literature review) of growth response to calcitriol and phosphate therapy","volume":"7","author":"Petersen","year":"1992","journal-title":"J. Bone Miner. Res."},{"key":"10.1016\/j.bone.2018.01.022_bb0125","doi-asserted-by":"crossref","first-page":"2601","DOI":"10.1002\/jbmr.2289","article-title":"Rapid skeletal turnover in a radiographic mimic of osteopetrosis","volume":"29","author":"Whyte","year":"2014","journal-title":"J. Bone Miner. Res."},{"key":"10.1016\/j.bone.2018.01.022_bb0130","doi-asserted-by":"crossref","first-page":"2515","DOI":"10.1002\/jbmr.130","article-title":"Elevated serum lactate dehydrogenase isoenzymes and aspartate transaminase distinguish Albers-Sch\u0151nberg disease (chloride channel 7 deficiency osteopetrosis) among the sclerosing bone disorders","volume":"25","author":"Whyte","year":"2010","journal-title":"J. Bone Miner. Res."},{"key":"10.1016\/j.bone.2018.01.022_bb0135","series-title":"Alkaline Phosphatase","author":"McComb","year":"1979"},{"key":"10.1016\/j.bone.2018.01.022_bb0145","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/0003-2697(83)90555-9","article-title":"A versatile cation-exchange procedure of measuring the seven major forms of vitamin B6 in biological samples","volume":"129","author":"Coburn","year":"1983","journal-title":"Anal. Biochem."},{"key":"10.1016\/j.bone.2018.01.022_bb0150","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.jchromb.2005.07.017","article-title":"Use of chlorite to improve HPLC detection of pyridoxal 5\u2032-phosphate","volume":"823","author":"Ericson","year":"2005","journal-title":"J. Chromatogr. B"},{"key":"10.1016\/j.bone.2018.01.022_bb0155","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/0003-2697(77)90510-3","article-title":"Analysis of inorganic pyrophosphate at the picomole level","volume":"83","author":"Cheung","year":"1977","journal-title":"Anal. Biochem."},{"key":"10.1016\/j.bone.2018.01.022_bb0160","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1111\/j.1749-6632.2010.05387.x","article-title":"Physiological role of alkaline phosphatase explored in hypophosphatasia","volume":"1192","author":"Whyte","year":"2010","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"10.1016\/j.bone.2018.01.022_bb0165","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1172\/JCI117814","article-title":"Alkaline phosphatase: placental and tissue nonspecific isoenzymes hydrolyze phospho-ethanolamine, inorganic pyrophosphate, and pyridoxal 5\u2032-phosphate (substrate accumulation in carriers of hypophosphatasia corrects during pregnancy)","volume":"95","author":"Whyte","year":"1995","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.bone.2018.01.022_bb0170","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1007\/BF01482855","article-title":"Excretion of acid phosphatase in urine as a sign of maturity in male adolescents","volume":"36","author":"Knorr","year":"1958","journal-title":"Klin. Wochenschr."},{"key":"10.1016\/j.bone.2018.01.022_bb0175","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1001\/archpedi.1948.02030020840003","article-title":"Hypophosphatasia: A new developmental anomaly","volume":"75","author":"Rathbun","year":"1948","journal-title":"Am. J. Dis. Child."},{"key":"10.1016\/j.bone.2018.01.022_bb0180","article-title":"Alkaline phosphatase: discovery and naming of our favorite enzyme","author":"Siller","year":"2017","journal-title":"J. Bone Miner. Res."},{"key":"10.1016\/j.bone.2018.01.022_bb0185","first-page":"3951","article-title":"Alkaline phosphatase (EC 3.1.3.1) in serum is inhibited by physiological concentrations of inorganic phosphate","volume":"83","author":"Coburn","year":"1998","journal-title":"J. Clin. Endocrinol. Metab."}],"container-title":["Bone"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S875632821830022X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S875632821830022X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2019,6,22]],"date-time":"2019-06-22T07:10:11Z","timestamp":1561187411000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S875632821830022X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5]]},"references-count":36,"alternative-id":["S875632821830022X"],"URL":"https:\/\/doi.org\/10.1016\/j.bone.2018.01.022","relation":{},"ISSN":["8756-3282"],"issn-type":[{"value":"8756-3282","type":"print"}],"subject":[],"published":{"date-parts":[[2018,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Hypophosphatasia: Biochemical hallmarks validate the expanded pediatric clinical nosology","name":"articletitle","label":"Article Title"},{"value":"Bone","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bone.2018.01.022","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2018 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}