Familial Hypocalciuric Hypercalcemia and Benefits of Genetic Confirmation: A Case Report and Review

ABSTRACT Objective: To differentiate familial hypocalciuric hypercalcemia (FHH), a rare condition, from primary hyperparathyroidism (PHPT), one of the most common causes of hypercalcemia, leading to avoidance of unnecessary surgical treatment; and also to review FHH. Methods: We present the history, physical, laboratory investigations, and clinical course of a 42-year-old woman who presented to our endocrinology office with hypercalcemia. An updated review on FHH is also provided. Results: FHH is a rare genetic disorder resulting from an inactivating mutation in the calcium-sensing receptor (CASR) gene. Inactivation of CASR causes increased parathyroid hormone (PTH) release with mild hypercalcemia. This condition should be differentiated from the other causes of hypercalcemia such as PHPT and malignancy. FHH does not usually have any signs, symptoms, or complications of hypercalcemia. Our patient presented with hypercalcemia with decreased urinary calcium excretion and was positive for a CASR mutation confirming FHH. This patient was able to avoid unnecessary parathyroid surgery based on these findings. Conclusion: FHH is diagnosed by mild hypercalcemia, normal or high PTH, and low urine calcium, and it is differentiated from primary PHPT by measuring the calcium/creatinine clearance ratio and finally genetic testing. FHH is a lifelong benign condition that does not require any treatment or surgery. Abbreviations: Ca calcium; CaSR calcium-sensing receptor; CASR calcium-sensing receptor gene; Cr creatinine; FHH familial hypocalciuric hypercalcemia; PTH parathyroid hormone; PHPT primary hyperparathyroidism