{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T13:57:58Z","timestamp":1773842278790,"version":"3.50.1"},"reference-count":10,"publisher":"The Endocrine Society","issue":"6","license":[{"start":{"date-parts":[[2023,12,7]],"date-time":"2023-12-07T00:00:00Z","timestamp":1701907200000},"content-version":"vor","delay-in-days":36,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,11,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Currently, no published cases report concomitant X-linked hypophosphatemia (XLH) and adult hypophosphatasia (HPP). Both diseases share clinical phenotypes that are almost indistinguishable. The correct diagnosis may be missed without a standardized laboratory and genetic testing approach. Pathogenic variants in the phosphate regulating endopeptidases homolog X-linked gene (PHEX) and the tissue-nonspecific alkaline phosphatase gene (ALPL) are genes that cause XLH and HPP, respectively. We describe a concomitant yet undescribed genetic pathogenic variant in a family. A 61-year-old woman was referred by orthopedic surgery for the presence of bilateral leg bowing and short stature during the assessment of knee surgery. The patient had a biochemical workup relevant for low serum phosphorus and 1,25-dihydroxy vitamin D and normal alkaline phosphatase (ALP). Genetic analysis revealed pathogenic variants in PHEX and ALPL. Her 42-year-old daughter shared identical symptoms and genetic variants with her mother. Both patients started conventional treatment for XLH with phosphorus and vitamin D, and the daughter later switched to burosumab-twza. Adult XLH and HPP may have similarities in clinical presentation but differ in some essential laboratory findings. Normal ALP levels helped direct our diagnosis toward XLH. However, the diagnosis was challenging due to the presence of concurrent variants in the genes involved. These variants illustrate the significant heterogeneity of the clinical expression.<\/jats:p>","DOI":"10.1210\/jcemcr\/luad151","type":"journal-article","created":{"date-parts":[[2023,12,7]],"date-time":"2023-12-07T22:30:42Z","timestamp":1701988242000},"source":"Crossref","is-referenced-by-count":1,"title":["A Novel Case of Concomitant PHEX and ALPL Mutation In a Family With Rickets"],"prefix":"10.1210","volume":"1","author":[{"given":"Carmen","family":"Polanco Santos","sequence":"first","affiliation":[{"name":"Endocrinology and Metabolism Institute, Cleveland Clinic Foundation , Cleveland, OH 44195 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3141-7517","authenticated-orcid":false,"given":"Juana","family":"Cordero Garate","sequence":"additional","affiliation":[{"name":"Jacobi Medical Center, Albert Einstein College of Medicine , Bronx, NY 10461 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leila","family":"Zeinab Khan","sequence":"additional","affiliation":[{"name":"Endocrinology and Metabolism Institute, Cleveland Clinic Foundation , Cleveland, OH 44195 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2023,12,7]]},"reference":[{"key":"2023120715331210500_luad151-B1","volume-title":"GeneReviews\u00ae [Internet]","author":"Ruppe","year":"1993"},{"issue":"1","key":"2023120715331210500_luad151-B2","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s13023-019-1014-8","article-title":"FGF23 And its role in X-linked hypophosphatemia-related morbidity","volume":"14","author":"Beck-Nielsen","year":"2019","journal-title":"Orphanet J Rare Dis"},{"issue":"12","key":"2023120715331210500_luad151-B3","doi-asserted-by":"crossref","first-page":"e1003975","DOI":"10.1371\/journal.pgen.1003975","article-title":"Parathyroid-specific deletion of klotho unravels a novel calcineurin-dependent FGF23 signaling pathway that regulates PTH secretion","volume":"9","author":"Olauson","year":"2013","journal-title":"PLoS Genet"},{"issue":"7","key":"2023120715331210500_luad151-B4","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1038\/s41581-019-0152-5","article-title":"Clinical practice recommendations for the diagnosis and management of X-linked hypophosphataemia","volume":"15","author":"Haffner","year":"2019","journal-title":"Nat Rev Nephrol"},{"issue":"3","key":"2023120715331210500_luad151-B5","first-page":"164","article-title":"Hypophosphatasia\u2014pathophysiology and treatment","volume":"8","author":"Mill\u00e1n","year":"2012","journal-title":"Actual En Osteol"},{"issue":"1","key":"2023120715331210500_luad151-B6","doi-asserted-by":"crossref","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"},{"issue":"1","key":"2023120715331210500_luad151-B7","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1186\/s13023-022-02572-7","article-title":"Identifying adult hypophosphatasia in the rheumatology unit","volume":"17","author":"Feurstein","year":"2022","journal-title":"Orphanet J Rare Dis"},{"issue":"12","key":"2023120715331210500_luad151-B8","doi-asserted-by":"crossref","first-page":"bvaa151","DOI":"10.1210\/jendso\/bvaa151","article-title":"X-Linked hypophosphatemia: a new era in management","volume":"4","author":"Dahir","year":"2020","journal-title":"J Endocr Soc"},{"issue":"8","key":"2023120715331210500_luad151-B9","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1002\/jbmr.3475","article-title":"A randomized, double-blind, placebo-controlled, phase 3 trial evaluating the efficacy of burosumab-twza, an anti-FGF23 antibody, in adults with X-linked hypophosphatemia: week 24 primary analysis: efficacy of burosumab-twza in aduts with XLH","volume":"33","author":"Insogna","year":"2018","journal-title":"J Bone Miner Res"},{"issue":"3","key":"2023120715331210500_luad151-B10","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1007\/s00223-019-00568-3","article-title":"Continued beneficial effects of burosumab-twza in adults with X-linked hypophosphatemia: results from a 24-week treatment continuation period after a 24-week double-blind placebo-controlled period","volume":"105","author":"Portale","year":"2019","journal-title":"Calcif Tissue Int"}],"container-title":["JCEM Case 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