Related Experiment Video
Updated: Sep 7, 2026
In Vivo Calcium Imaging in C. elegans Body Wall Muscles
Published on: October 20, 2019
Case Report: Unusual Presentations of Loss-of-Function Mutations of the Calcium-Sensing Receptor
Serena Palmieri1, Giorgia Grassi1, Vito Guarnieri2
1Unit of Endocrinology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy.
Background:
In 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 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.
Conclusions:
These 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.
Insights
Heterozygous inactivating Calcium Sensing Receptor (CaSR) mutations present diverse hypercalcemic syndromes beyond FHH. These cases highlight varied phenotypes and the need for personalized treatment strategies.
Area of Science:
- Endocrinology
- Genetics
Background:
- Heterozygous loss-of-function mutations in the Calcium Sensing Receptor (CaSR) gene are linked to hypercalcemic disorders.
- These include familial hypocalciuric hypercalcemia (FHH), neonatal severe primary hyperparathyroidism (NSHPT), and primary hyperparathyroidism (PHPT).
Observation:
- Two distinct cases of heterozygous inactivating CaSR mutations are presented.
- Case 1: NSHPT due to a de novo p.(ArgR185Gln) CaSR mutation, treated with cinacalcet and surgery.
- Case 2: A 37-year-old woman with PHPT, hypercalcemia, and nephrocalcinosis due to a novel p.(Pro393Arg) CaSR mutation, treated with parathyroidectomy.
Findings:
- The clinical spectrum of CaSR inactivating mutations is broader than previously recognized.
- Inactivating CaSR mutations can manifest with phenotypes different from typical FHH, presenting unique clinical challenges.
Implications:
- These findings underscore the importance of considering CaSR mutations in unexplained hypercalcemic syndromes.
- Individualized therapeutic approaches are crucial for managing patients with diverse CaSR mutation phenotypes and associated complications.
Related Concept Videos
01:27Feedback Regulation of Calcium Concentration
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
01:16Calmodulin-dependent Signaling
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...