Three inherited disorders of calcium sensing

Abstract

Three distinct disorders of calcium homeostasis can result from mutations in the gene encoding the human calcium-sensing receptors (CASR; MIM 145980). One form of autosomal dominant familial hypocalciuric hypercalcemia results from the heterozygous state of inactivating mutations in the CASR gene. Neonatal severe hyperparathyroidism results from homozygosity for inactivating mutations in the CASR gene. The severe phenotype demonstrates the fundamental role the calcium-sensing receptor plays in parathyroid function. Activating mutations can lead to autosomal dominant hypocalcemia. The role of the calcium-sensing receptor in the kidney, brain, and other organs in health and disease awaits clarification.