[Familial hypoparathyroidism due to activating mutations in the calcium-sensing receptor gene]

The cloning of the extracellular calcium-sensing receptor(CaSR) has helped to define a key component in the control of the calcium homeostasis. Gain-of-function mutations in the CaSR gene were identified as the cause of autosomal dominant hypocalcemia (ADH). This clinical condition is compatible with hypoparathyroidism because of low PTH levels compared with serum calcium levels. Until now, 21 missense mutations of the CaSR were identified as a cause of hypoparathyroidism (HP). Mutations present in transmembrane domain may produce more severe hypocalcemia than those present in other domains. We emphasize that it is important to differentiate ADH from PTH-deficient HP, because treatment with vitamin D to correct the hypocalcemia in the former may lead to more severe hypercalciuria, nephrocalcinosis, and renal impairment.