{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T16:37:16Z","timestamp":1789663036130,"version":"4.0.1"},"reference-count":10,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2024,6,1]],"date-time":"2024-06-01T00:00:00Z","timestamp":1717200000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Clark and Mildred Cox Inherited Metabolic Bone Disease Research Endowed Fund at the Foundation for Barnes-Jewish Hospital"},{"DOI":"10.13039\/100011781","name":"Shriners Hospitals for Children","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011781","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,7,23]]},"abstract":"<jats:title>Vignette<\/jats:title>\n               <jats:p>Hypophosphatasia (HPP) is the dento-osseous disorder caused by deactivating mutation(s) of ALPL, the gene that encodes the \u201ctissue-nonspecific\u201d isoenzyme of alkaline phosphatase (TNSALP). In HPP, 3 natural substrates of cell-surface TNSALP accumulate extracellularly; phosphoethanolamine (PEA), inorganic pyrophosphate (PPi), and pyridoxal 5\u2032-phosphate (PLP). Hypophosphatasemia together with elevated plasma levels of PEA, PPi, and PLP comprise its biochemical signature. PPi can inhibit mineralization and in extracellular excess can impair bone and tooth hardening and perhaps explain weak muscle. Autosomal dominant or autosomal recessive inheritance from among more than 400 mutations of ALPL largely accounts for HPP\u2019s broad-ranging severity, greatest among all skeletal diseases. Pediatric HPP spans life-threatening perinatal and infantile forms, childhood forms, and odonto-HPP selectively featuring premature loss of deciduous teeth. ALPL gene testing and TNSALP supplementation therapy have bolstered familiarity with HPP, but there are new considerations for diagnosis. Herein, diagnosis of a boy\u2019s mild childhood HPP was delayed by missteps involving his medical and dental history, physical examination, radiographic findings, and clinical laboratory studies. We review how pediatric HPP is now identified. Prompt diagnosis while appreciating the broad-ranging severity of HPP underlies the safe and effective management of this inborn-error-of-metabolism.<\/jats:p>","DOI":"10.1093\/jbmr\/zjae098","type":"journal-article","created":{"date-parts":[[2024,6,21]],"date-time":"2024-06-21T17:41:40Z","timestamp":1718991700000},"page":"655-660","source":"Crossref","is-referenced-by-count":11,"title":["Pediatric hypophosphatasia: avoid diagnosis missteps!"],"prefix":"10.1093","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8755-8490","authenticated-orcid":false,"given":"Michael P","family":"Whyte","sequence":"first","affiliation":[{"name":"Division of Bone and Mineral Diseases , Department of Internal Medicine, ; St. Louis, MO 63110 , United States"},{"name":"Washington University School of Medicine at Barnes-Jewish Hospital , Department of Internal Medicine, ; St. Louis, MO 63110 , United States"},{"name":"Center for Metabolic Bone Disease and Molecular Research, Shriners Hospitals for Children-St. Louis ; St. Louis, MO 63110 , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William H","family":"McAlister","sequence":"additional","affiliation":[{"name":"Pediatric Radiology Section, Mallinckrodt Institute of Radiology at St. Louis Children\u2019s Hospital, Washington University School of Medicine ; St. Louis, MO 63110 , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen E","family":"Mack","sequence":"additional","affiliation":[{"name":"Center for Metabolic Bone Disease and Molecular Research, Shriners Hospitals for Children-St. Louis ; St. Louis, MO 63110 , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9267-4413","authenticated-orcid":false,"given":"Steven","family":"Mumm","sequence":"additional","affiliation":[{"name":"Division of Bone and Mineral Diseases , Department of Internal Medicine, ; St. Louis, MO 63110 , United States"},{"name":"Washington University School of Medicine at Barnes-Jewish Hospital , Department of Internal Medicine, ; St. Louis, MO 63110 , United States"},{"name":"Center for Metabolic Bone Disease and Molecular Research, Shriners Hospitals for Children-St. Louis ; St. Louis, MO 63110 , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine L","family":"Madson","sequence":"additional","affiliation":[{"name":"Center for Metabolic Bone Disease and Molecular Research, Shriners Hospitals for Children-St. Louis ; St. Louis, MO 63110 , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,6,21]]},"reference":[{"issue":"4","key":"2024072411363384400_ref1","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"},{"issue":"2","key":"2024072411363384400_ref2","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1002\/jbmr.3225","article-title":"Alkaline phosphatase: discovery and naming of our favorite enzyme","volume":"33","author":"Siller","year":"2018","journal-title":"J Bone Miner Res"},{"key":"2024072411363384400_ref3","volume-title":"Genetics of Bone Biology and Skeletal Disease","author":"Whyte","edition":"3rd"},{"key":"2024072411363384400_ref4","doi-asserted-by":"crossref","first-page":"117033","DOI":"10.1016\/j.bone.2024.117033","article-title":"Pyridoxine challenge reflects pediatric hypophosphatasia severity and thereby examines tissue-nonspecific alkaline phosphatase's role in vitamin B6 metabolism","volume":"181","author":"Whyte","year":"2024","journal-title":"Bone"},{"key":"2024072411363384400_ref5","article-title":"Hyperphosphatemia with Low FGF7 and Normal FGF23 and SFRP4 Levels in the Circulation Characterizes Pediatric Hypophosphatasia","volume-title":"Bone","author":"Whyte"},{"key":"2024072411363384400_ref6","doi-asserted-by":"crossref","first-page":"116947","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"},{"key":"2024072411363384400_ref7","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.bone.2018.01.022","article-title":"Hypophosphatasia: biochemical hallmarks validate the expanded pediatric clinical nosology","volume":"110","author":"Whyte","year":"2018","journal-title":"Bone"},{"key":"2024072411363384400_ref8","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"},{"issue":"5","key":"2024072411363384400_ref9","doi-asserted-by":"crossref","first-page":"868","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","volume":"33","author":"Whyte","year":"2018","journal-title":"J Bone Miner Res"},{"issue":"1","key":"2024072411363384400_ref10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00198-023-06843-2","article-title":"Proposed diagnostic criteria for the diagnosis of hypophosphatasia in children and adolescents: results from the HPP International Working Group","volume":"35","author":"Rush","year":"2023","journal-title":"Osteoporos Int"}],"container-title":["Journal of Bone and Mineral 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