A Newly Identified Mutation in the Calcium-Sensing Receptor Gene Causing Familial Hypocalciuric Hypercalcemia: A Case Report

ABSTRACT Objective: To emphasize the importance of genetic testing of the calcium-sensing receptor (CaSR) in cases where biochemical tests fail to differentiate between primary hyperparathyroidism (PHPT) and familial hypocalciuric hypercalcemia (FHH). Methods: We present the clinical history and laboratory findings of a patient and review related literature. Results: A 35-year-old male patient presented with asymptomatic hypercalcemia. His clinical picture and laboratory findings were not consistent with either PHPT or FHH but were more suspicious for FHH. A significant family history of hypercalcemia of unknown cause in his father and uncle along with a strong suspicion of FHH necessitated the genetic testing of CaSR in the patient and his father. Testing revealed a newly identified mutation variant, c.533A>C (p. N178T), that has not been reported previously as a cause of FHH. Conclusion: FHH is a rare, lifelong, benign condition. A combination of clinical suspicion, biochemical testing, and in some cases genetic analysis, is required to differentiate PHPT from FHH and thus spare patients with FHH from unnecessary operative treatment. Abbreviations: AP2S1 = adaptor-related protein complex 2, sigma 1 subunit; CaSR = calcium-sensing receptor; FHH = familial hypocalciuric hypercalcemia; Gα11 G-protein subunit α11; OMIM = Online Mendelian Inheritance in Man; PHPT = primary hyperparathyroidism; PTH = parathyroid hormone; RR = reference range; UCCR = urinary calcium to creatinine clearance ratio