Activating Mutations of the Calcium-Sensing Receptor: Management of Hypocalcemia

Activating mutations of the calcium-sensing receptor (CaR) can cause isolated hypoparathyroidism. Treatment of hypocalcemia in these patients remains to be optimized, because the use of 1-hydroxylated vitamin D3 derivatives can cause hypercalciuria and nephrocalcinosis. We identified activating CaR mutations in 8 (42%) of 19 unrelated probands with isolated hypoparathyroidism. The severity of hypocalcemic symptoms at diagnosis was independent of age, mutation type, or mode of inheritance but was related to the degree of hypocalcemia; serum Ca was 1.97 ± 0.08, 1.82 ± 0.14, and 1.54 ± 0.22 mmol/liter, respectively, in asymptomatic (n = 7), mildly symptomatic (n= 8), and severely symptomatic patients (n = 6). Hypocalcemia segregated with the CaR mutation, but no phenotype-genotype relationships were identified. Fourteen patients received regular 1-hydroxylated vitamin D3 treatment (mean duration, 7.2 ± 4.9 yr). Nine had hypercalciuric episodes, which were associated with nephrocalcinosis in eight cases. Seru...