Inherited Diseases of the Calcium-Sensing Receptor: Impact on Parathyroid and Renal Function

Publisher Summary This chapter gives an overview on inherited diseases of the calcium-sensing receptor (CaR or CaSR) that have significant impact on parathyroid and renal function. One of the diseases, neonatal severe primary hyperparathyroidism (NSHPT), typically presents within the first six months of life. Affected infants have severe, symptomatic, parathyroid hormone (PTH)-dependent hypercalcemia as well as the bony changes of severe hyperparathyroidism. Infants with NSHPT can also manifest polyuria, dehydration, hypotonia, and failure to thrive. A prominent component of the disorder is the hyperparathyroid bone disease, which can lead to multiple fractures of the long bones and other skeletal sites. Patients with autosomal dominant form of hypocalcemia/hypoparathyroidism are commonly asymptomatic, similar to the majority of patients with familial hypocalciuric hypercalcemia (FHH). Some exhibit neuromuscular irritability, seizures, and calcification of the basal ganglia, complications commonly seen in other forms of hypoparathyroidism in which the CaR gene is normal. During febrile episodes, patients with autosomal dominant hypoparathyroidism (ADH), particularly children, can exhibit symptomatic hypocalcemia and, in some cases, develop seizures. Patients with ADH appear particularly susceptible to complications during treatment with Ca 2+ and vitamin D analogs aimed at increasing their serum Ca 2+ concentrations toward normal. They are especially prone to developing renal complications, including nephrocalcinosis, nephrolithiasis, and renal impairment during treatment of ADH patients with Ca2+and vitamin D. The renal complications observed during treatment of ADH generally occur in a setting in which the clinician has tried to correct the serum Ca 2+ concentration to or close to the normal range. Treatment with Ca 2+ supplements and vitamin D metabolites should be reserved for those patients with symptomatic ADH.