{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:04:28Z","timestamp":1768349068514,"version":"3.49.0"},"reference-count":10,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T00:00:00Z","timestamp":1724112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100013220","name":"Ultragenyx","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013220","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,9,26]]},"abstract":"<jats:title>Vignette<\/jats:title>\n               <jats:p>Familial hypocalciuric hypercalcemia (FHH) is typically a benign condition characterized by elevated serum calcium, low urinary calcium excretion, and non-suppressed circulating levels of parathyroid hormone (PTH), usually requiring no intervention. FHH is inherited in an autosomal-dominant manner. Three subtypes are described, representing variants in genes with critical roles in extracellular calcium-sensing. FHH1, due to heterozygous inactivating variants in the calcium-sensing receptor gene (CASR), accounts for the majority of cases. FHH2, due to variants in GNA11, encoding the \u03b1-subunit of the downstream signaling protein, G11, is the rarest form of FHH. FHH3, resulting from variants in AP2S1, may present with a more pronounced phenotype than FHH1 or FHH2. We describe herein a newborn girl presenting with in utero femoral fractures, hypercalcemia, hypophosphatemia, and elevated circulating PTH. She was diagnosed with mild hyperparathyroidism and provided supplemental phosphate upon hospital discharge. However, serum calcium and PTH remained elevated at 5\u00a0mo of age. The combination of low-calcium formula and cinacalcet improved the biochemical profile. No pathogenic variants in the coding region of CASR were identified; subsequent whole exome sequencing revealed a G-\u2009&amp;gt;\u2009T transition at c.44 (p.R15L) in AP2S1. Family studies identified this variant in the father and an affected brother. The mother was unexpectedly found to be hypocalcemic and was diagnosed with idiopathic hypoparathyroidism. This case demonstrates successful treatment of FHH3 using a low-calcium formula to limit dietary calcium availability and cinacalcet to modify PTH levels.<\/jats:p>","DOI":"10.1093\/jbmr\/zjae137","type":"journal-article","created":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T08:47:03Z","timestamp":1724143623000},"page":"1406-1411","source":"Crossref","is-referenced-by-count":1,"title":["Familial hypocalciuric hypercalcemia in an infant: diagnosis and management quandaries"],"prefix":"10.1093","volume":"39","author":[{"given":"Bracha","family":"Goldsweig","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Baystate Medical Center, Springfield MA01107,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rukiye Sena","family":"Turk Yilmaz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (Endocrinology), Yale University School of Medicine , New Haven CT06520,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Apoorva","family":"Ravindranath Waikar","sequence":"additional","affiliation":[{"name":"Virginia Commonwealth University Health System , Division of Pediatric Endocrinology, Richmond VA23298,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"Brownstein","sequence":"additional","affiliation":[{"name":"Manton Center for Orphan Disease Research , Division of Genetics and Genomics, , Boston MA 02115,","place":["United States"]},{"name":"Boston Children\u2019s Hospital , Division of Genetics and Genomics, , Boston MA 02115,","place":["United States"]},{"name":"Department of Pediatrics, Harvard Medical School , Boston, MA 02115,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1328-6768","authenticated-orcid":false,"given":"Thomas O","family":"Carpenter","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (Endocrinology), Yale University School of Medicine , New Haven CT06520,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,8,20]]},"reference":[{"issue":"2","key":"2024092612155573000_ref1","doi-asserted-by":"crossref","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"},{"issue":"7","key":"2024092612155573000_ref2","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1016\/0092-8674(93)90617-Y","article-title":"Mutations in the human Ca(2+)-sensing receptor gene cause familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism","volume":"75","author":"Pollak","year":"1993","journal-title":"Cell"},{"issue":"1","key":"2024092612155573000_ref3","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/ng.2492","article-title":"Mutations in AP2S1 cause familial hypocalciuric hypercalcemia type 3","volume":"45","author":"Nesbit","year":"2013","journal-title":"Nat Genet"},{"issue":"5","key":"2024092612155573000_ref4","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.1210\/jc.2015-3442","article-title":"Familial Hypocalciuric hypercalcemia types 1 and 3 and primary hyperparathyroidism: similarities and differences","volume":"101","author":"Vargas-Poussou","year":"2016","journal-title":"J Clin Endocrinol Metab"},{"issue":"18","key":"2024092612155573000_ref5","doi-asserted-by":"crossref","first-page":"5079","DOI":"10.1093\/hmg\/ddv226","article-title":"Adaptor protein-2 sigma subunit mutations causing familial hypocalciuric hypercalcaemia type 3 (FHH3) demonstrate genotype-phenotype correlations, codon bias and dominant-negative effects","volume":"24","author":"Hannan","year":"2015","journal-title":"Hum Mol Genet"},{"issue":"12","key":"2024092612155573000_ref6","doi-asserted-by":"crossref","first-page":"E2022","DOI":"10.1210\/jc.2013-2571","article-title":"Identification of AP2S1 mutation and effects of low calcium formula in an infant with hypercalcemia and hypercalciuria","volume":"98","author":"Fujisawa","year":"2013","journal-title":"J Clin Endocrinol Metab"},{"issue":"2","key":"2024092612155573000_ref7","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1111\/j.1365-2796.2006.01684.x","article-title":"Normalization of serum calcium by cinacalcet in a patient with hypercalcaemia due to a de novo inactivating mutation of the calcium-sensing receptor","volume":"260","author":"Timmers","year":"2006","journal-title":"J Intern Med"},{"issue":"14","key":"2024092612155573000_ref8","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1056\/NEJMc1511646","article-title":"Cinacalcet for symptomatic hypercalcemia caused by AP2S1 mutations","volume":"374","author":"Howles","year":"2016","journal-title":"N Engl J Med"},{"issue":"5","key":"2024092612155573000_ref9","doi-asserted-by":"crossref","first-page":"R189","DOI":"10.1530\/EJE-15-1028","article-title":"Genetics in endocrinology: gain and loss of function mutations of the calcium-sensing receptor and associated proteins: current treatment concepts","volume":"174","author":"Mayr","year":"2016","journal-title":"Eur J Endocrinol"},{"issue":"2","key":"2024092612155573000_ref10","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1210\/clinem\/dgad494","article-title":"Cinacalcet reverses short QT interval in familial hypocalciuric hypercalcemia type 1","volume":"109","author":"Cuny","year":"2024","journal-title":"J Clin Endocrinol 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