{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T23:25:23Z","timestamp":1779233123611,"version":"3.51.4"},"reference-count":95,"publisher":"The Endocrine Society","issue":"4","funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Neonatal severe hyperparathyroidism (NSHPT) is rare and potentially lethal. It is usually from homozygous or heterozygous germline-inactivating CASR variant(s). NSHPT shows a puzzling range of serum calcium and parathyroid hormone (PTH) levels. Optimal therapy is unclear.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Evidence acquisition<\/jats:title>\n                  <jats:p>We categorized genotype\/phenotype pairings related to CASRs. For the 2 pairings in NSHPT, each of 57 cases of neonatal severe hyperparathyroidism required calcium, PTH, upper normal PTH, and dosage of a germline pathogenic CASR variant.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Evidence synthesis<\/jats:title>\n                  <jats:p>Homozygous and heterozygous NSHPT are 2 among a spectrum of 9 genotype\/phenotype pairings relating to CASRs and NSHPT. For the 2 NSHPT pairings, expressions differ in CASR allelic dosage, CASR variant severity, and sufficiency of maternofetal calcium fluxes. Homozygous dosage of CASR variants was generally more aggressive than heterozygous. Among heterozygotes, high-grade CASR variants in vitro were more pathogenic in vivo than low-grade variants. Fetal calcium insufficiency as from maternal hypoparathyroidism caused fetal secondary hyperparathyroidism, which persisted and was reversible in neonates. Among NSHPT pairings, calcium and PTH were higher in CASR homozygotes than in heterozygotes. Extreme hypercalcemia (above 4.5 mM; normal 2.2\u20132.6 mM) is a robust biomarker, occurring only in homozygotes (83% of that pairing). It could occur during the first week.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>In NSHPT pairings, the homozygotes for pathogenic CASR variants show higher calcium and PTH levels than heterozygotes. Calcium levels above 4.5 mM among NSHPT are frequent and unique only to most homozygotes. This cutoff supports early and robust diagnosis of CASR dosage. Thereby, it promotes definitive total parathyroidectomy in most homozygotes.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgz233","type":"journal-article","created":{"date-parts":[[2019,11,28]],"date-time":"2019-11-28T16:10:40Z","timestamp":1574957440000},"page":"1061-1078","source":"Crossref","is-referenced-by-count":39,"title":["Neonatal Severe Hyperparathyroidism: Novel Insights From Calcium, PTH, and the <i>CASR<\/i> Gene"],"prefix":"10.1210","volume":"105","author":[{"given":"Stephen J","family":"Marx","sequence":"first","affiliation":[{"name":"Office of the Scientific Director, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Bethesda, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ninet","family":"Sinaii","sequence":"additional","affiliation":[{"name":"Biostatistics and Clinical Epidemiology Service, National Institutes of Health Clinical Center, Bethesda, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2019,11,28]]},"reference":[{"issue":"6","key":"2021122210032946000_CIT0001","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/S0022-3468(86)80219-6","article-title":"Primary hyperparathyroidism in infancy","volume":"21","author":"Ross","year":"1986","journal-title":"J Pediatr Surg."},{"issue":"3","key":"2021122210032946000_CIT0002","doi-asserted-by":"crossref","first-page":"R127","DOI":"10.1530\/JME-16-0124","article-title":"Disorders of the calcium-sensing receptor and partner proteins: insights into the molecular basis of calcium homeostasis","volume":"57","author":"Hannan","year":"2016","journal-title":"J Mol Endocrinol."},{"key":"2021122210032946000_CIT0003","article-title":"Disorders of the calcium-sensing receptor: familial hypocalciuric hypercalcemia and autosomal dominant hypocalcemia.","volume-title":"UpToDate","author":"Brown","year":"2019"},{"issue":"5","key":"2021122210032946000_CIT0004","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":"1","key":"2021122210032946000_CIT0005","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1002\/jbmr.3650","article-title":"Evolution of our understanding of the hyperparathyroid syndromes: a historical perspective","volume":"34","author":"Marx","year":"2019","journal-title":"J Bone Miner Res."},{"issue":"2","key":"2021122210032946000_CIT0006","first-page":"205","article-title":"Primary neonatal hyperparathyroidism: a devastating neurodevelopmental disorder if left untreated","volume":"10","author":"Cole","year":"1990","journal-title":"J Craniofac Genet Dev Biol."},{"issue":"3","key":"2021122210032946000_CIT0007","first-page":"P041","article-title":"Severe but not neonatally lethal. 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Scand."},{"issue":"12","key":"2021122210032946000_CIT0010","doi-asserted-by":"crossref","first-page":"2768","DOI":"10.1093\/hmg\/dds105","article-title":"Identification of 70 calcium-sensing receptor mutations in hyper- and hypo-calcaemic patients: evidence for clustering of extracellular domain mutations at calcium-binding sites","volume":"21","author":"Hannan","year":"2012","journal-title":"Hum Mol Genet."},{"issue":"5","key":"2021122210032946000_CIT0011","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1530\/EJE-16-0223","article-title":"Heterozygous inactivating CaSR mutations causing neonatal hyperparathyroidism: function, inheritance and phenotype","volume":"175","author":"Glaudo","year":"2016","journal-title":"Eur J Endocrinol."},{"issue":"10","key":"2021122210032946000_CIT0012","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1002\/jbmr.2516","article-title":"Polyclonality of parathyroid tumors in neonatal severe 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kindreds","volume":"60","author":"Marx","year":"1981","journal-title":"Medicine (Baltimore)."},{"issue":"5","key":"2021122210032946000_CIT0016","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1210\/jcem-65-5-1039","article-title":"Distribution of serum calcium values in patients with familial benign hypercalcemia (hypocalciuric hypercalcemia): evidence for a discrete genetic defect","volume":"65","author":"Rajala","year":"1987","journal-title":"J Clin Endocrinol Metab."},{"issue":"6","key":"2021122210032946000_CIT0017","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1097\/MED.0b013e32834c3c7c","article-title":"Familial hypocalciuric hypercalcaemia: a review","volume":"18","author":"Christensen","year":"2011","journal-title":"Curr Opin Endocrinol Diabetes Obes."},{"issue":"5","key":"2021122210032946000_CIT0018","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence 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Metab."},{"issue":"2","key":"2021122210032946000_CIT0021","doi-asserted-by":"crossref","first-page":"R37","DOI":"10.1530\/EJE-18-0541","article-title":"Management of endocrine disease: hypoparathyroidism in pregnancy: review and evidence-based recommendations for management","volume":"180","author":"Khan","year":"2019","journal-title":"Eur J Endocrinol."},{"issue":"7","key":"2021122210032946000_CIT0022","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1093\/pch\/7.7.455","article-title":"Congenital rickets caused by maternal vitamin D deficiency","volume":"7","author":"Innes","year":"2002","journal-title":"Paediatr Child Health."},{"issue":"3","key":"2021122210032946000_CIT0023","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.siny.2013.01.005","article-title":"Maternal vitamin D deficiency: fetal and neonatal implications","volume":"18","author":"Kovacs","year":"2013","journal-title":"Semin Fetal Neonatal 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Pathol."},{"issue":"6","key":"2021122210032946000_CIT0027","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1016\/0002-9343(84)90852-0","article-title":"Parathyroid glands in familial benign hypercalcemia (familial hypocalciuric hypercalcemia)","volume":"76","author":"Law","year":"1984","journal-title":"Am J Med."},{"issue":"5","key":"2021122210032946000_CIT0028","first-page":"2042","article-title":"Familial hypercalcemia and hypercalciuria caused by a novel mutation in the cytoplasmic tail of the calcium receptor","volume":"85","author":"Carling","year":"2000","journal-title":"J Clin Endocrinol Metab."},{"issue":"3","key":"2021122210032946000_CIT0029","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1067\/msy.2002.120674","article-title":"Parathyroidectomy in familial hypercalcemia with clinical characteristics of primary hyperparathyroidism and familial hypocalciuric 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hypercalcemia in a 9-year-old Brazilian girl due to a novel inactivating mutation of the calcium-sensing receptor","volume":"89","author":"Miyashiro","year":"2004","journal-title":"J Clin Endocrinol Metab."},{"issue":"4","key":"2021122210032946000_CIT0036","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1046\/j.1365-2265.1999.00729.x","article-title":"An adult patient with severe hypercalcaemia and hypocalciuria due to a novel homozygous inactivating mutation of calcium-sensing receptor","volume":"50","author":"Chikatsu","year":"1999","journal-title":"Clin Endocrinol (Oxf)."},{"issue":"9","key":"2021122210032946000_CIT0037","first-page":"2594","article-title":"Familial hypocalciuric hypercalcemia associated with mutation in the human Ca(2+)-sensing receptor gene","volume":"80","author":"Aida","year":"1995","journal-title":"J Clin Endocrinol Metab."},{"issue":"11","key":"2021122210032946000_CIT0038","doi-asserted-by":"crossref","first-page":"4372","DOI":"10.1210\/jc.2008-2484","article-title":"A novel loss-of-function mutation, Gln459Arg, of the calcium-sensing receptor gene associated with apparent autosomal recessive inheritance of familial hypocalciuric hypercalcemia","volume":"94","author":"Lietman","year":"2009","journal-title":"J Clin Endocrinol Metab."},{"issue":"6","key":"2021122210032946000_CIT0039","doi-asserted-by":"crossref","first-page":"E1146","DOI":"10.1210\/jc.2013-3593","article-title":"A homozygous CaSR mutation causing a FHH phenotype completely masked by vitamin D deficiency presenting as rickets","volume":"99","author":"Szczawinska","year":"2014","journal-title":"J Clin Endocrinol Metab."},{"issue":"10","key":"2021122210032946000_CIT0040","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1002\/ccr3.1074","article-title":"Making (mis) sense of asymptomatic marked hypercalcemia in pregnancy","volume":"5","author":"Maltese","year":"2017","journal-title":"Clin Case Rep."},{"issue":"11","key":"2021122210032946000_CIT0041","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1007\/s40618-017-0710-2","article-title":"Familial hypocalciuric hypercalcemia type 1 due to a novel homozygous mutation of the calcium-sensing receptor gene","volume":"40","author":"Borsari","year":"2017","journal-title":"J Endocrinol Invest."},{"issue":"1","key":"2021122210032946000_CIT0042","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1177\/0300985810395725","article-title":"Early embryonic lethality in genetically engineered mice: diagnosis and phenotypic analysis","volume":"49","author":"Papaioannou","year":"2012","journal-title":"Vet Pathol."},{"issue":"1","key":"2021122210032946000_CIT0043","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1186\/s13059-015-0792-0","article-title":"TLE6 mutation causes the earliest known human embryonic lethality","volume":"16","author":"Alazami","year":"2015","journal-title":"Genome Biol."},{"issue":"1","key":"2021122210032946000_CIT0044","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/0002-9343(85)90455-3","article-title":"Familial hypocalciuric hypercalcemia. Mild expression of the gene in heterozygotes and severe expression in homozygotes","volume":"78","author":"Marx","year":"1985","journal-title":"Am J Med."},{"issue":"2","key":"2021122210032946000_CIT0045","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1002\/(SICI)1096-8628(19970808)71:2<202::AID-AJMG16>3.0.CO;2-I","article-title":"Neonatal severe hyperparathyroidism, secondary hyperparathyroidism, and familial hypocalciuric hypercalcemia: multiple different phenotypes associated with an inactivating Alu insertion mutation of the calcium-sensing receptor gene","volume":"71","author":"Cole","year":"1997","journal-title":"Am J Med Genet."},{"issue":"1","key":"2021122210032946000_CIT0046","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1172\/JCI119137","article-title":"In vivo and in vitro characterization of neonatal hyperparathyroidism resulting from a de novo, heterozygous mutation in the Ca2+-sensing receptor gene: normal maternal calcium homeostasis as a cause of secondary hyperparathyroidism in familial benign hypocalciuric hypercalcemia","volume":"99","author":"Bai","year":"1997","journal-title":"J Clin Invest."},{"key":"2021122210032946000_CIT0047","first-page":"493","article-title":"Marked hypercalcemia in a five month old male associated with heterozygous point mutation in the calcium-sensing receptor gene","volume-title":"Program and Abstracts of the 80th Annual Meeting of the Endocrinology Society","author":"Arunchaiya","year":"1998"},{"issue":"12","key":"2021122210032946000_CIT0048","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."},{"key":"2021122210032946000_CIT0049","article-title":"Familial hypocalciuric hypercalcemia type 3 presenting as neonatal bone disease: a dual treatment approach","volume-title":"Program and Abstracts of the 98th Annual Meeting of the Endocrine Society","author":"Goldsweig","year":"2016"},{"issue":"6","key":"2021122210032946000_CIT0050","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/j.pan.2019.07.045","article-title":"Cinacalcet sustainedly prevents pancreatitis in a child with a compound heterozygous SPINK1\/AP2S1 mutation","volume":"19","author":"Scheers","year":"2019","journal-title":"Pancreatology."},{"issue":"5","key":"2021122210032946000_CIT0051","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1111\/j.1582-4934.2007.00096.x","article-title":"Structure and function of the human calcium-sensing receptor: insights from natural and engineered mutations and allosteric modulators","volume":"11","author":"Hu","year":"2007","journal-title":"J Cell Mol Med."},{"key":"2021122210032946000_CIT0052","doi-asserted-by":"crossref","first-page":"e13662","DOI":"10.7554\/eLife.13662","article-title":"Structural mechanism of ligand activation in human calcium-sensing receptor","volume":"5","author":"Geng","year":"2016","journal-title":"Elife"},{"issue":"5","key":"2021122210032946000_CIT0053","doi-asserted-by":"crossref","first-page":"e1600241","DOI":"10.1126\/sciadv.1600241","article-title":"Structural basis for regulation of human calcium-sensing receptor by magnesium ions and an unexpected tryptophan derivative co-agonist","volume":"2","author":"Zhang","year":"2016","journal-title":"Sci Adv."},{"issue":"4","key":"2021122210032946000_CIT0054","doi-asserted-by":"crossref","first-page":"E707","DOI":"10.1210\/jc.2010-1306","article-title":"Neonatal hyperparathyroidism with a heterozygous calcium-sensing receptor (CASR) R185Q mutation: clinical benefit from cinacalcet","volume":"96","author":"Reh","year":"2011","journal-title":"J Clin Endocrinol Metab."},{"key":"2021122210032946000_CIT0055","first-page":"150040","article-title":"Successful treatment of neonatal severe hyperparathyroidism with cinacalcet in two patients","volume":"2015","author":"Fisher","year":"2015","journal-title":"Endocrinol Diabetes Metab Case Rep."},{"issue":"3","key":"2021122210032946000_CIT0056","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1515\/jpem-2018-0307","article-title":"Cinacalcet therapy in an infant with an R185Q calcium-sensing receptor mutation causing hyperparathyroidism: a case report and review of the literature","volume":"32","author":"Forman","year":"2019","journal-title":"J Pediatr Endocrinol Metab."},{"issue":"8","key":"2021122210032946000_CIT0057","first-page":"2716","article-title":"Two novel missense mutations in calcium-sensing receptor gene associated with neonatal severe hyperparathyroidism","volume":"82","author":"Kobayashi","year":"1997","journal-title":"J Clin Endocrinol Metab."},{"issue":"2-3","key":"2021122210032946000_CIT0058","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/0021-9150(91)90084-G","article-title":"Familial defective apolipoprotein B-100: haplotype analysis of the arginine(3500)\u2013\u2013glutamine mutation","volume":"88","author":"Rauh","year":"1991","journal-title":"Atherosclerosis."},{"issue":"7463","key":"2021122210032946000_CIT0059","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/nature12477","article-title":"Signatures of mutational processes in human cancer","volume":"500","author":"Alexandrov","year":"2013","journal-title":"Nature."},{"issue":"1","key":"2021122210032946000_CIT0060","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1038\/cdd.2017.180","article-title":"Why are there hotspot mutations in the TP53 gene in human cancers?","volume":"25","author":"Baugh","year":"2018","journal-title":"Cell Death Differ."},{"key":"2021122210032946000_CIT0061","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/1471-2350-13-69","article-title":"High prevalence of arginine to glutamine substitution at 98, 141 and 162 positions in troponin I (TNNI3) associated with hypertrophic 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