Neonatal Hyperparathyroidism with a Heterozygous Calcium-Sensing Receptor (CASR) R185Q Mutation: Clinical Benefit from Cinacalcet

Context: Neonatal hyperparathyroidism can be caused by a heterozygous inactivating mutation in the calcium-sensing receptor. Calcimimetics, allosteric activators of the calcium-sensing receptor, may provide an effective means of reducing PTH secretion in such patients. Objective/Patient: The objective of the study was to identify the molecular defect and to monitor the postnatal course of a 1-wk-old infant with elevated blood ionized calcium, serum PTH, and alkaline phosphatase and low calcium excretion. The parents were normocalcemic. Methods: CASR gene mutation analysis was performed on genomic DNA of the proband and her parents. The infant was treated initially with pamidronate and then cinacalcet. Results: A heterozygous mutation (R185Q, CGA>CAA) in exon 4 of the CASR gene was identified in the proband. The CASR gene of both parents was normal. At 1 wk of age, iv fluids and furosemide were initiated, but hypercalcemia, hyperparathyroidism, and low calcium excretion persisted. At 2 wk of age, a single iv dose of pamidronate resulted in hypocalcemia and further increase in PTH levels, but hypercalcemia recurred within 1 wk. At 3 wk of age, a single oral dose of cinacalcet resulted in decreased PTH levels at 2 h; blood-ionized calcium reached a nadir at 10 h. Three days later daily cinacalcet was initiated, resulting in normalization of ionized calcium. The suppression of serum PTH and reduction in total serum calcium was maintained long term. Conclusions: In neonatal hyperparathyroidism secondary to presumed de novo heterozygous CASR mutation, treatment with cinacalcet decreases PTH secretion and serum calcium levels and mitigates the need for parathyroidectomy. (J Clin Endocrinol Metab 96: E707-E712, 2011)