{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:49:54Z","timestamp":1787237394652,"version":"build-2736575974"},"reference-count":16,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Hypercalcemia in infancy is rare and often presents with nonspecific clinical signs, making early recognition challenging. This report describes two infants with severe symptomatic hypercalcemia due to distinct etiologies and highlights the diagnostic value of sterile pyuria as an early clinical clue.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      Both infants presented with nonspecific symptoms, including poor feeding, irritability, constipation, and sterile pyuria. In the first infant the diagnosis of Williams-Beuren syndrome had been established earlier, while the second infant had been previously healthy. Both had demonstrated sonographic evidence of nephrocalcinosis. Laboratory evaluation revealed markedly elevated serum calcium levels (up to 4.73 mmol\/L), hypercalciuria, and suppressed PTH concentrations in both cases. Standard treatment of hypercalcemia was ineffective, while a single dose of zoledronic acid led to normalization of calcium levels and complete resolution of symptoms. Subsequent genetic testing in the second infant identified a biallelic pathogenic variant in the\n                      <jats:italic>CYP24A1<\/jats:italic>\n                      gene, confirming the diagnosis of idiopathic infantile hypercalcemia type 1. During follow-up, neither patient experienced recurrence of hypercalcemia, and renal ultrasound showed improvement or stabilization of nephrocalcinosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Sterile pyuria accompanied by nonspecific symptoms may be an early indicator of hypercalcemia in infants and should prompt calcium evaluation. To our knowledge, this is the first report linking sterile pyuria directly to hypercalcemia in this age group. Zoledronic acid can effectively normalize calcium levels in refractory pediatric hypercalcemia. This report adds to the limited evidence regarding zoledronic acid use in infants with Williams\u2013Beuren syndrome and idiopathic infantile hypercalcemia type 1.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1799236","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T04:11:15Z","timestamp":1774843875000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Case Report: Two infants with hypercalcemia of rare and distinct etiologies"],"prefix":"10.3389","volume":"17","author":[{"given":"Ivona Butorac","family":"Ahel","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Clinical Hospital Centre Rijeka","place":["Rijeka, Croatia"]},{"name":"Faculty of Medicine, University of Rijeka","place":["Rijeka, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vereniki","family":"Andritsos","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Clinical Hospital Centre Rijeka","place":["Rijeka, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u0110ur\u0111ica","family":"Ko\u0161uljandi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Clinical Hospital Centre Rijeka","place":["Rijeka, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sre\u0107ko","family":"Severinski","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Clinical Hospital Centre Rijeka","place":["Rijeka, Croatia"]},{"name":"Faculty of Medicine, University of Rijeka","place":["Rijeka, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Je\u0161i\u0107","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Clinical Hospital Centre Rijeka","place":["Rijeka, Croatia"]},{"name":"Faculty of Medicine, University of Rijeka","place":["Rijeka, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina Lovrinovi\u0107","family":"Grozdani\u0107","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Clinical Hospital Centre Rijeka","place":["Rijeka, Croatia"]},{"name":"Faculty of Medicine, University of Rijeka","place":["Rijeka, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina Baraba","family":"Dekani\u0107","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Clinical Hospital Centre Rijeka","place":["Rijeka, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jurica","family":"Jambrovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Clinical Hospital Centre Rijeka","place":["Rijeka, Croatia"]},{"name":"Faculty of Medicine, University of Rijeka","place":["Rijeka, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iva Bili\u0107","family":"\u010ca\u010de","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Clinical Hospital Centre Rijeka","place":["Rijeka, Croatia"]},{"name":"Faculty of Medicine, University of Rijeka","place":["Rijeka, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,30]]},"reference":[{"key":"B1","volume-title":"Approach to Hypercalcemia","author":"Goltzman","year":"2023"},{"key":"B2","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1007\/s00467-021-05082-z","article-title":"Genetic causes of neonatal and infantile hypercalcaemia","volume":"37","author":"Gorvin","year":"2022","journal-title":"Pediatr Nephrol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.3296","article-title":"Hypercalcemic disorders in children","volume":"32","author":"Stokes","year":"2017","journal-title":"J Bone Miner Res"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1097\/MOP.0b013e32833b7c23","article-title":"Hypercalcemia in children and adolescents","volume":"22","author":"Lietman","year":"2010","journal-title":"Curr Opin Pediatr"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s13730-025-01010-4","article-title":"Williams syndrome presenting as infantile hypercalcemia with acute kidney injury: a case report","volume":"14","author":"Park","year":"2025","journal-title":"CEN Case Rep"},{"key":"B6","doi-asserted-by":"publisher","first-page":"e3131","DOI":"10.1002\/brb3.3131","article-title":"A case report of Williams syndrome with main clinical manifestation of hypercalcemia and gastrointestinal bleeding as the main clinical manifestations, and with an accompanying literature review","volume":"13","author":"Meng","year":"2023","journal-title":"Brain Behav"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.4306","article-title":"Differential diagnosis of vitamin D\u2013related hypercalcemia using serum vitamin D metabolite profiling","volume":"36","author":"Kaufmann","year":"2021","journal-title":"J Bone Miner Res"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.3135","article-title":"Improved screening test for idiopathic infantile hypercalcemia confirms residual levels of serum 24,25-(OH)2 D3 in affected patients","volume":"32","author":"Kaufmann","year":"2017","journal-title":"J Bone Miner Res"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1177\/2333794X21993712","article-title":"The differential diagnosis of sterile pyuria in pediatric patients: A review","volume":"8","author":"Bendig","year":"2021","journal-title":"Glob Pediatr Health"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2024.01.011","article-title":"Sterile pyuria in the modern era: clinical spectrum and diagnostic yield","volume":"137","author":"Muthukumar","year":"2024","journal-title":"Am J Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1053\/j.ackd.2014.12.001","article-title":"Clinical approach to sterile pyuria","volume":"22","author":"Grewal","year":"2015","journal-title":"Adv Chronic Kidney Dis"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfaa178","article-title":"Long-term outcome of the survivors of infantile hypercalcaemia with CYP24A1 and SLC34A1 mutations","volume":"36","author":"Janiec","year":"2021","journal-title":"Nephrol Dial Transplant"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2018.00240","article-title":"Pamidronate rescue therapy for hypercalcemia in a child with williams syndrome","volume":"9","author":"Sanjad","year":"2018","journal-title":"Front Endocrinol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1515\/jpem-2023-0212","article-title":"Successful treatment of hypercalcemia in a Chinese patient with a novel homozygous mutation in the CYP24A1 gene using zoledronic acid: a case report","volume":"36","author":"Zheng","year":"2023","journal-title":"J Pediatr Endocrinol Metab"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1515\/cclm-2018-1208","article-title":"CYP24A1 and SLC34A1 genetic defects associated with idiopathic infantile hypercalcemia: from genotype to phenotype","volume":"57","author":"De Paolis","year":"2019","journal-title":"Clin Chem Lab Med"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2023.106301","article-title":"Rifampin monotherapy for children with idiopathic infantile hypercalcemia","volume":"231","author":"Lenherr-Taube","year":"2023","journal-title":"J Steroid Biochem Mol Biol"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1799236\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T04:11:23Z","timestamp":1774843883000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1799236\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,30]]},"references-count":16,"alternative-id":["10.3389\/fendo.2026.1799236"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1799236","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,30]]},"article-number":"1799236"}}