{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T16:14:46Z","timestamp":1777133686076,"version":"3.51.4"},"reference-count":16,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T00:00:00Z","timestamp":1655856000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T00:00:00Z","timestamp":1655856000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20K19673"],"award-info":[{"award-number":["20K19673"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21K19504"],"award-info":[{"award-number":["21K19504"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Endocr Disord"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Familial hypocalciuric hypercalcemia (FHH) is a rare autosomal dominant disease, which requires differential diagnosis from relatively common primary hyperparathyroidism (PHPT) in order to avoid unnecessary surgery.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Case presentation<\/jats:title>\n                <jats:p>A 16-year-old female had been followed by the department of psychosomatic medicine at our institution. Throughout the follow-up period, her plasma calcium levels were high, plasma Pi levels were relatively low, and plasma intact PTH was relatively high. She was referred to our department to determine the cause of her hypercalcemia. Her 24\u00a0h urinary calcium excretion was as low as 100\u00a0mg\/day, and calcium creatinine clearance ratio was below 0.01. Moreover, she had a family history of hypercalcemia (proband, her brother, and her father). The genetic testing for her family revealed that she, her brother, and her father were definitively diagnosed with FHH type 1 due to the heterozygous calcium-sensing receptor mutation (NM_00388:4:c.164C\u2009&gt;\u2009T:p.Pro55Leu).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>We experienced a 16-year-old female with FHH, in whom genetic testing identified the heterozygous calcium-sensing receptor mutation (NM_00388:4:c.164C\u2009&gt;\u2009T:p.Pro55Leu) as pathogenic, permitting a definitive diagnosis of FHH type 1. The genetic testing for calcium sensing receptor is beneficial to distinguish asymptomatic primary hyperparathyroidism from FHH.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12902-022-01077-5","type":"journal-article","created":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T11:03:26Z","timestamp":1655895806000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A case of familial hypocalciuric hypercalcemia type 1 due to CASR p.Pro55Leu mutation"],"prefix":"10.1186","volume":"22","author":[{"given":"Akira","family":"Sumida","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9837-6238","authenticated-orcid":false,"given":"Katsumi","family":"Iizuka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takehiro","family":"Kato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanyan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sodai","family":"Kubota","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saki","family":"Kubota-Okamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teruaki","family":"Sakurai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshinori","family":"Imaizumi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshihiro","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masami","family":"Mizuno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ken","family":"Takao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takuo","family":"Hirota","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuya","family":"Suwa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukio","family":"Horikawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mayumi","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yusuke","family":"Seino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsushi","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daisuke","family":"Yabe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,6,22]]},"reference":[{"issue":"3","key":"1077_CR1","doi-asserted-by":"publisher","first-page":"270","DOI":"10.7861\/clinmedicine.17-3-270","volume":"17","author":"JJO Turner","year":"2017","unstructured":"Turner JJO. Hypercalcaemia - presentation and management. Clin Med (Lond). 2017;17(3):270\u20133.","journal-title":"Clin Med (Lond)"},{"issue":"5","key":"1077_CR2","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1016\/j.beem.2018.05.004","volume":"32","author":"JY Lee","year":"2018","unstructured":"Lee JY, Shoback DM. Familial hypocalciuric hypercalcemia and related disorders. Best Pract Res Clin Endocrinol Metab. 2018;32(5):609\u201319.","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"issue":"4","key":"1077_CR3","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1007\/s002230001201","volume":"68","author":"J Hinnie","year":"2001","unstructured":"Hinnie J, Bell E, McKillop E, Gallacher S. The prevalence of familial hypocalciuric hypercalcemia. Calcif Tissue Int. 2001;68(4):216\u20138.","journal-title":"Calcif Tissue Int"},{"issue":"5","key":"1077_CR4","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1111\/j.1365-2265.2008.03259.x","volume":"69","author":"SE Christensen","year":"2008","unstructured":"Christensen SE, Nissen PH, Vestergaard P, Heickendorff L, Brixen K, et al. Discriminative power of three indices of renal calcium excretion for the distinction between familial hypocalciuric hypercalcaemia and primary hyperparathyroidism: a follow-up study on methods. Clin Endocrinol (Oxf). 2008;69(5):713\u201320.","journal-title":"Clin Endocrinol (Oxf)"},{"key":"1077_CR5","doi-asserted-by":"crossref","unstructured":"Vargas-Poussou R, Mansour-Hendili L, Baron S, Bertocchio JP, Travers C, Simian C, et al. Familial Hypocalciuric Hypercalcemia Types 1 and 3 and Primary Hyperparathyroidism: Similarities and Differences. J Clin Endocrinol Metab.\u00a02016;101(5):2185\u201395.","DOI":"10.1210\/jc.2015-3442"},{"issue":"3","key":"1077_CR6","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1016\/S0889-8529(18)30362-1","volume":"18","author":"Heath H 3rd","year":"1989","unstructured":"Heath H 3rd. Familial benign (hypocalciuric) hypercalcemia. A troublesome mimic of mild primary hyperparathyroidism. Endocrinol Metab Clin North Am. 1989;18(3):723\u201340.","journal-title":"Endocrinol Metab Clin North Am"},{"issue":"5","key":"1077_CR7","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","volume":"17","author":"S Richards","year":"2015","unstructured":"Richards S, Aziz N, Bale S, Bick D, Das S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405\u201324.","journal-title":"Genet Med"},{"issue":"11","key":"1077_CR8","doi-asserted-by":"publisher","first-page":"3933","DOI":"10.1210\/jc.2017-01606","volume":"102","author":"SJ Marx","year":"2017","unstructured":"Marx SJ. Calcimimetic use in familial hypocalciuric hypercalcemia-a perspective in endocrinology. J Clin Endocrinol Metab. 2017;102(11):3933\u20136.","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"1077_CR9","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1002\/1098-1004(200010)16:4<281::AID-HUMU1>3.0.CO;2-A","volume":"16","author":"GN Hendy","year":"2000","unstructured":"Hendy GN, D\u2019Souza-Li L, Yang B, Canaff L, Cole DE. Mutations of the calcium-sensing receptor (CASR) in familial hypocalciuric hypercalcemia, neonatal severe hyperparathyroidism, and autosomal dominant hypocalcemia. Hum Mutat. 2000;16(4):281\u201396.","journal-title":"Hum Mutat"},{"issue":"12","key":"1077_CR10","doi-asserted-by":"publisher","first-page":"2768","DOI":"10.1093\/hmg\/dds105","volume":"21","author":"FM Hannan","year":"2012","unstructured":"Hannan FM, Nesbit MA, Zhang C, Cranston T, Curley AJ, et al. Identification of 70 calcium-sensing receptor mutations in hyper- and hypo-calcaemic patients: evidence for clustering of extracellular domain mutations at calcium-binding sites. Hum Mol Genet. 2012;21(12):2768\u201378.","journal-title":"Hum Mol Genet"},{"issue":"8","key":"1077_CR11","doi-asserted-by":"publisher","first-page":"1860","DOI":"10.1172\/JCI118987","volume":"98","author":"SH Pearce","year":"1996","unstructured":"Pearce SH, Bai M, Quinn SJ, Kifor O, Brown EM, Thakker RV. Functional characterization of calcium-sensing receptor mutations expressed in human embryonic kidney cells. J Clin Invest. 1996;98(8):1860\u20136.","journal-title":"J Clin Invest"},{"issue":"4","key":"1077_CR12","doi-asserted-by":"publisher","first-page":"1819","DOI":"10.1210\/jc.2008-2430","volume":"95","author":"V Guarnieri","year":"2010","unstructured":"Guarnieri V, Canaff L, Yun FH, Scillitani A, Battista C, et al. Calcium-sensing receptor (CASR) mutations in hypercalcemic states: studies from a single endocrine clinic over three years. J Clin Endocrinol Metab. 2010;95(4):1819\u201329.","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"1077_CR13","doi-asserted-by":"publisher","first-page":"2683","DOI":"10.1172\/JCI118335","volume":"96","author":"SH Pearce","year":"1995","unstructured":"Pearce SH, Trump D, Wooding C, Besser GM, Chew SL, et al. Calcium-sensing receptor mutations in familial benign hypercalcemia and neonatal hyperparathyroidism. J Clin Invest. 1995;96(6):2683\u201392.","journal-title":"J Clin Invest"},{"issue":"4","key":"1077_CR14","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1097\/00019606-200112000-00006","volume":"10","author":"S Fukumoto","year":"2001","unstructured":"Fukumoto S, Chikatsu N, Okazaki R, Takeuchi Y, Tamura Y, et al. Inactivating mutations of calcium-sensing receptor results in parathyroid lipohyperplasia. Diagn Mol Pathol. 2001;10(4):242\u20137.","journal-title":"Diagn Mol Pathol"},{"issue":"2","key":"1077_CR15","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1046\/j.1365-2265.2003.01696.x","volume":"58","author":"F Cetani","year":"2003","unstructured":"Cetani F, Pardi E, Borsari S, Tonacchera M, Morabito E, et al. Two Italian kindreds with familial hypocalciuric hypercalcaemia caused by loss-of-function mutations in the calcium-sensing receptor (CaR) gene: functional characterization of a novel CaR missense mutation. Clin Endocrinol (Oxf). 2003;58(2):199\u2013206.","journal-title":"Clin Endocrinol (Oxf)"},{"issue":"7929","key":"1077_CR16","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1016\/S0140-6736(75)92736-1","volume":"2","author":"RJ Walton","year":"1975","unstructured":"Walton RJ, Bijvoet OL. Nomogram for derivation of renal threshold phosphate concentration. Lancet. 1975;2(7929):309\u201310.","journal-title":"Lancet"}],"container-title":["BMC Endocrine Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12902-022-01077-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12902-022-01077-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12902-022-01077-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T11:04:17Z","timestamp":1655895857000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcendocrdisord.biomedcentral.com\/articles\/10.1186\/s12902-022-01077-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,22]]},"references-count":16,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["1077"],"URL":"https:\/\/doi.org\/10.1186\/s12902-022-01077-5","relation":{},"ISSN":["1472-6823"],"issn-type":[{"value":"1472-6823","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,22]]},"assertion":[{"value":"20 August 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 June 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 June 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"We obtained approval from the ethics committee of Gifu University Graduate School of Medicine (Approval number 2020-201). The patient and her relatives provided written consent to participate in genetic screening for hereditary hypercalcemia.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"After she became at 18 years old, we obtained written informed consent of this case report from both herself and her parent. Genetic testing was carried out after counseling by a clinical genetic specialist. Her parents and her brothers were above 20 years old and we obtained written informed consent of this case report from themselves. We also obtained written informed consent for genetic test for her and her families. The patient and her families also gave written consent for their personal or clinical details along with any identifying images to be published in this study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to publication"}},{"value":"All authors have no conflict of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"164"}}