{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T15:34:32Z","timestamp":1765812872833,"version":"3.48.0"},"reference-count":25,"publisher":"The Endocrine Society","issue":"1","license":[{"start":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T00:00:00Z","timestamp":1764806400000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mild to moderate elevations of calcium may be asymptomatic and therefore remain undiagnosed until detected incidentally or when an aggravating factor exacerbates the hypercalcemia, causing recognizable symptoms. We report a unique case of a 26-year-old male with persistent hypercalcemia, nephrolithiasis, suppressed PTH, normal PTH-related protein, and hypercalciuria but no etiological diagnosis despite an exhaustive workup. Genetic analysis revealed a novel homozygous missense pathogenic variant of the CYP24A1 gene, crucial for vitamin D metabolism. Mutations in this gene have been shown to cause hypercalcemia, due to decreased catabolism of 1,25-dihydroxyvitamin D3, resulting in increased calcium absorption, hypercalcemia, and hypercalciuria, without elevated PTH levels. Over 16 months of follow-up, the hypercalcemia remained mild to moderate, with instructions to restrict supplemental vitamin D and dietary calcium. He also received fluconazole 50\u2005mg daily and magnesium glycinate 850\u2005mg 12 hourly for 3 months. Calcium levels fell from 12.7\u2005mg\/dL (8.2-10.3\u2005mg\/dL) (SI: 3.1\u2005mmol\/L [2.1-2.6\u2005mmol\/L]) to 9.4\u2005mg\/dL (SI: 2.3\u2005mmol\/L). This case underscores the importance of considering CYP24A1 pathogenic variant in unexplained hypercalcemia. Identification of a novel variant expands the genetic landscape of hypercalcemia and supports further exploration of targeted therapies.<\/jats:p>","DOI":"10.1210\/jcemcr\/luaf284","type":"journal-article","created":{"date-parts":[[2025,11,15]],"date-time":"2025-11-15T12:56:12Z","timestamp":1763211372000},"source":"Crossref","is-referenced-by-count":0,"title":["A Challenging Case of Hypercalcemia Caused by a Novel Homozygous Variant Missense Mutation in the\n                    <i>CYP24A1<\/i>\n                    Gene"],"prefix":"10.1210","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3429-7354","authenticated-orcid":false,"given":"Tasnim","family":"Ahsan","sequence":"first","affiliation":[{"name":"Medicell Institute of Diabetes, Endocrinology & Metabolism , Karachi 75600, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0521-1387","authenticated-orcid":false,"given":"Muhammad","family":"Yahya","sequence":"additional","affiliation":[{"name":"Medicell Institute of Diabetes, Endocrinology & Metabolism , Karachi 75600, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7468-522X","authenticated-orcid":false,"given":"Heer","family":"Dilawar","sequence":"additional","affiliation":[{"name":"Medicell Institute of Diabetes, Endocrinology & Metabolism , Karachi 75600, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6437-7511","authenticated-orcid":false,"given":"Ameet","family":"Kumar","sequence":"additional","affiliation":[{"name":"Medicell Institute of Diabetes, Endocrinology & Metabolism , Karachi 75600, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roomana","family":"Siddiqui","sequence":"additional","affiliation":[{"name":"Endocrinology Department, OMI Hospital , OMI Hospital, Karachi 74400, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2025,12,4]]},"reference":[{"key":"2025121510320229600_luaf284-B1","first-page":"176","volume-title":"Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism","author":"Shane","year":"2006","edition":"6th ed"},{"issue":"16","key":"2025121510320229600_luaf284-B2","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.1001\/jama.2022.18331","article-title":"Hypercalcemia: a review","volume":"328","author":"Walker","year":"2022","journal-title":"JAMA"},{"issue":"11","key":"2025121510320229600_luaf284-B3","doi-asserted-by":"crossref","first-page":"483","DOI":"10.4103\/1947-2714.170600","article-title":"Hypercalcemia of malignancy: an update 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