{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:11:12Z","timestamp":1772118672984,"version":"3.50.1"},"reference-count":16,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T00:00:00Z","timestamp":1691452800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["asbmr.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JBMR Plus"],"published-print":{"date-parts":[[2023,9]]},"abstract":"ABSTRACT<\/jats:title>\n \n Hypervitaminosis D as a cause of hypercalcemia may be due to vitamin D intoxication, granulomatous diseases, or abnormalities of vitamin D metabolism. The\n CYP24A1<\/jats:italic>\n gene encodes for the 24\u2010hydroxylase enzyme, which is responsible for the catabolism of 25\u2010hydroxyvitamin D (25(OH)D) and 1,25\u2010dihydroxyvitamin D (1,25(OH)2D). Mutations in\n CYP24A1<\/jats:italic>\n can result in elevated 1,25(OH)2D causing parathyroid hormone (PTH)\u2010independent hypercalcemia, hypercalciuria, nephrolithiasis, and nephrocalcinosis. We present the cases of two siblings exhibiting hypercalcemia secondary to a\n CYP24A1<\/jats:italic>\n loss\u2010of\u2010function mutation. Case 1 presented initially with PTH\u2010dependent hypercalcemia, with localization of a left upper parathyroid adenoma on parathyroid technetium sestamibi (\n 99m<\/jats:sup>\n Tc\u2010MIBI) uptake study. Despite parathyroidectomy (180\u2009mg adenoma), hypercalcemia, hypercalciuria, and low normal PTH levels persisted. A repeat parathyroid\n 99m<\/jats:sup>\n Tc\u2010MIBI uptake study localized a second adenoma and a right inferior parathyroidectomy was performed (170\u2009mg adenoma). PTH subsequently became undetectable, however hypercalcemia and hypercalciuria persisted. A new presentation of PTH\u2010independent hypercalcemia found to be secondary to a\n CYP24A1<\/jats:italic>\n loss\u2010of\u2010function mutation in his sibling, Case 2, signaled the underlying cause. Cascade testing confirmed both siblings were homozygous for the pathogenic variant c.1186C>T, p.Arg396Trp (R396W) of\n CYP24A1<\/jats:italic>\n (NM_000782.5). In clinical practice\n CYP24A1<\/jats:italic>\n loss\u2010of\u2010function mutations should be considered in patients presenting with PTH\u2010independent hypercalcemia, hypercalciuria, and 1,25(OH)2D levels in the upper normal or elevated range. Although in our case assays of 24,25(OH)2D were not available, calculation of the 25(OH)D:24,25(OH)2D ratio can assist in the diagnostic process. Possible treatments to manage the risk of hypercalcemia in patients with a\n CYP24A1<\/jats:italic>\n loss\u2010of\u2010function mutation include avoidance of vitamin D oversupplementation and excessive sun exposure. Hydration and bisphosphonate therapy can be useful in managing the hypercalcemia. Although not utilized in our cases, treatment with ketoconazole, fluconazole, and rifampicin have been described as potential therapeutic options. \u00a9 2023 The Authors.\n JBMR Plus<\/jats:italic>\n published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.\n <\/jats:p>","DOI":"10.1002\/jbm4.10788","type":"journal-article","created":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T00:45:10Z","timestamp":1691541910000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Hypervitaminosis D Secondary to a\n \n CYP24A1<\/i>\n <\/scp>\n Loss\u2010of\u2010Function Mutation: An Unusual Cause of Hypercalcemia in Two Siblings"],"prefix":"10.1093","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4957-1483","authenticated-orcid":false,"given":"Lucy","family":"Collins","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Diabetes Western Health Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma","family":"Boehm","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes Western Health Melbourne Victoria Australia"},{"name":"University of Melbourne Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"Luxford","sequence":"additional","affiliation":[{"name":"Royal North Shore Hospital Kolling Institute St Leonards New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roderick","family":"Clifton\u2010Bligh","sequence":"additional","affiliation":[{"name":"Royal North Shore Hospital Kolling Institute St Leonards New South Wales Australia"},{"name":"Department of Endocrinology Royal North Shore Hospital St Leonards New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vivian","family":"Grill","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes Western Health Melbourne Victoria Australia"},{"name":"University of Melbourne Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,8,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2016.04.001"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1103864"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-016-3615-6"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-1935"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22981"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R031534"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-4388"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014-4387"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-21-0713"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-020-00738-8"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ando.2016.03.002"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00240-016-0923-4"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.141.7.7579"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2016-4048"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgac315"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.05360512"}],"container-title":["JBMR 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