Case Report: Unusual Presentations of Loss-of-Function Mutations of the Calcium-Sensing Receptor.

Serena Palmieri,Cristina Eller-Vainicher,Vito Guarnieri,Iacopo Chiodini,Maura Arosio,Giorgia Grassi

doi:10.3389/fmed.2021.809067

Abstract

BackgroundIn recent years, heterozygous loss-of-function mutations of the Calcium Sensing Receptor gene (CaSR) were implicated in different hypercalcemic syndromes besides familial hypocalciuric hypercalcemia (FHH), including neonatal severe primary hyperparathyroidism (NSHPT) and primary hyperparathyroidism (PHPT).Cases presentationHere we describe two unusual presentations of heterozygous inactivating CaSR mutations. Case 1: a case of NSHPT due to a de novo, p.(ArgR185Gln) CaSR mutation and successfully treated with cinacalcet monotherapy for 8 years until definitive surgical resolution. Case 2: a 37 years-old woman with PHPT complicated with hypercalcemia and nephrocalcinosis with a novel heterozygous p.(Pro393Arg) CaSR mutation and cured with parathyroidectomy.ConclusionsThese cases reinforce the fact that the clinical spectrum of inactivating mutations of the CaSR has widened and, although carrying a mutation suggestive of FHH, some patients may have different clinical phenotypes and complications requiring individualized therapies.

Highlights

The Calcium-Sensing Receptor (CaSR), a plasma membrane G protein-coupled receptor, provides the major mechanism for the detection of extracellular calcium concentration in several cell types and modulates parathyroid hormone (PTH) release in the parathyroid glands and urinary calcium reabsorption and excretion in the kidney [1,2,3,4,5]
We describe two unusual presentations of heterozygous loss-of-function Calcium Sensing Receptor gene (CaSR) mutations: a case of neonatal severe primary hyperparathyroidism (NSHPT) successfully treated with long term cinacalcet monotherapy until definitive surgical resolution and a case of complicated primary hyperparathyroidism (PHPT) with heterozygous CaSR mutation cured with PTx
We described the unusual occurrence of heterozygous missense mutations in the CaSR, which is typical for familial hypocalciuric hypercalcemia (FHH), in two patients with biochemical and histological findings consistent with NSHPT and PHPT respectively

Summary

Background

Heterozygous loss-of-function mutations of the Calcium Sensing Receptor gene (CaSR) were implicated in different hypercalcemic syndromes besides familial hypocalciuric hypercalcemia (FHH), including neonatal severe primary hyperparathyroidism (NSHPT) and primary hyperparathyroidism (PHPT). Cases presentation: Here we describe two unusual presentations of heterozygous inactivating CaSR mutations. Case 1: a case of NSHPT due to a de novo, p.(ArgR185Gln) CaSR mutation and successfully treated with cinacalcet monotherapy for 8 years until definitive surgical resolution. Case 2: a 37 years-old woman with PHPT complicated with hypercalcemia and nephrocalcinosis with a novel heterozygous p.(Pro393Arg) CaSR mutation and cured with parathyroidectomy

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ETHICS STATEMENT