The calcium sensing receptor (CASR) plays an important role in calcium homeostasis. CASR is present at particularly high levels in the parathyroid glands and kidneys.
Binding of calcium by CASR in the parathyroid glands results in down regulation of parathyroid hormone (PTH) synthesis, while binding of calcium to the CASR in the kidneys results in upregulation of renal calcium excretion. These simultaneous opposite reactions lead to tight control of plasma calcium levels.
To date over 100 different alterations in the CASR gene have been identified. Inactivating mutations result in under-sensing of calcium concentrations and consequent PTH overproduction and secretion. This leads to familial hypocalciuric hypercalcemia (FHH) which is characterized by mildly-to-moderately elevated plasma calcium levels, normal or slightly low phosphate, and urinary calcium excretion that is low for the degree of hypercalcemia. PTH is within the reference range or modestly elevated.
Activating mutations lead to over-sensing of calcium, resulting in suppression of PTH secretion and consequently hypoparathyroidism. All of the activating mutations described so far have been inherited in an autosomal dominant manner.
A CASR mutation should be identified in an affected family member before predictive testing of family members is recommended. CASR mutations are detected by DNA sequencing.
Specimen requirement is a lavender top (EDTA) tube of whole blood.
References
Tőke J, Czirják G, Enyedi P, Tóth M. Rare diseases caused by abnormal calcium sensing and signalling. Endocrine. 2021 Mar;71(3):611-617. doi: 10.1007/s12020-021-02620-5.
Hannan FM, Thakker RV. Calcium-sensing receptor (CaSR) mutations and disorders of calcium, electrolyte and water metabolism. Best Pract Res Clin Endocrinol Metab. 2013 Jun;27(3):359-71. doi: 10.1016/j.beem.2013.04.007.
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