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Novel homozygous inactivating mutation of the calcium-sensing receptor gene (CASR) in neonatal severe hyperparathyroidism-lack of effect of cinacalcet

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dc.contributor.authorBEREKET, ABDULLAH
dc.contributor.authorsAtay, Zeynep; Bereket, Abdullah; Haliloglu, Belma; Abali, Saygin; Ozdogan, Tutku; Altuncu, Emel; Canaff, Lucie; Vilaca, Tatiane; Wong, Betty Y. L.; Cole, David E. C.; Hendy, Geoffrey N.; Turan, Serap
dc.date.accessioned2022-03-13T12:46:32Z
dc.date.available2022-03-13T12:46:32Z
dc.date.issued2014
dc.description.abstractBackground: NSHPT is a life-threatening disorder caused by homozygous inactivating calcium-sensing receptor (CASR) mutations. In some cases, the CaSR allosteric activator, cinacalcet, may reduce serum PTH and calcium levels, but surgery is the treatment of choice. Objective: To describe a case of NSHPT unresponsive to cinacalcet. Patient and Results: A 23-day-old girl was admitted with hypercakemia, hypotonia, bell-shaped chest and respiratory distress. The parents were first-degree cousins once removed. Serum Ca was 4.75 mmol/l (N: 2.10-2.62), P: 0.83 mmol/l (1.55-2.64), PTH: 1096 pg/ml (9-52) and urinary Ca/Cr ratio: 0.5 mg/mg. First, calcitonin was given (10 IU/kg x 4/day), and then 2 days later, pamidronate (0.5 mg/kg) for 2 days. Doses of cinacalcet were given daily from day 28 of life starting at 30 mg/m(2) and increasing to 90 mg/m(2) on day 43. On day 33, 6 days after pamidronate, serum Ca levels had fallen to 2.5 mmol/l but, thereafter, rose to 5 mmol/l despite the cinacalcet Total parathyroidectomy was performed at day 45. Hungry bone disease after surgery required daily Ca replacement and calcitriol for 18 days. At 3 months, the girl was mildly hypercalcemic, with no supplementation, and at 6 months, she developed hypocalcemia and has since been maintained on Ca and calcitriol. By CASR mutation analysis, the infant was homozygous and both parents heterozygous for a deletion-frameshift mutation. Conclusion: The predicted nonfunctional CaSR is consistent with lack of response to cinacalcet, but total parathyroidectomy was successful. An empiric trial of the drug and/or prompt mutation testing should help minimize the period of unnecessary pharmacotherapy. (C) 2014 Elsevier Inc. All rights reserved.
dc.identifier.doi10.1016/j.bone.2014.04.010
dc.identifier.eissn1873-2763
dc.identifier.issn8756-3282
dc.identifier.pubmed24735972
dc.identifier.urihttps://hdl.handle.net/11424/237938
dc.identifier.wosWOS:000337011500015
dc.language.isoeng
dc.publisherELSEVIER SCIENCE INC
dc.relation.ispartofBONE
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectNeonatal severe hyperparathyroidism
dc.subjectCalcium-sensing receptor
dc.subjectMutation
dc.subjectCalcimimetic
dc.subjectFAMILIAL HYPOCALCIURIC HYPERCALCEMIA
dc.subjectPAMIDRONATE
dc.subjectRESCUE
dc.titleNovel homozygous inactivating mutation of the calcium-sensing receptor gene (CASR) in neonatal severe hyperparathyroidism-lack of effect of cinacalcet
dc.typearticle
dspace.entity.typePublication
local.avesis.id25960221-78e0-4fc2-adda-9dd9f3d47caa
local.import.packageSS17
local.indexed.atWOS
local.indexed.atSCOPUS
local.indexed.atPUBMED
local.journal.numberofpages6
oaire.citation.endPage107
oaire.citation.startPage102
oaire.citation.titleBONE
oaire.citation.volume64
relation.isAuthorOfPublication669e9474-4e39-453f-a4bc-4ede9cb5abac
relation.isAuthorOfPublication.latestForDiscovery669e9474-4e39-453f-a4bc-4ede9cb5abac

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