Objective: To review the pathophysiology, clinical features, diagnosis, and management options for benign familial hypocalciuric hypercalcemia.
Methods: We present a systematic summary of benign familial hypocalciuric hypercalcemia after review of the current available literature.
Results: Benign familial hypocalciuric hypercalcemia is an autosomal dominant condition characterized by lifelong hypercalcemia, relative hypocalciuria, and inappropriately elevated parathyroid hormone. It is caused by a loss-of-function mutation in the calcium-sensing receptor gene (CASR). Benign familial hypocalciuric hypercalcemia is important clinically because it can be difficult to distinguish from primary hyperparathyroidism. It is a benign condition, and affected patients should be advised against parathyroidectomy. The incidence of complications associated with primary hyperparathyroidism, like osteopenia and nephrolithiasis, is not increased in persons with benign familial hypocalciuric hypercalcemia, and the rates are similar to those in the general population. Rarely, a severe form of this disease, namely neonatal severe primary hyperparathyroidism is seen in infants with homozygous CASR mutations.
Conclusions: Benign familial hypocalciuric hypercalcemia is a small but important cause of hypercalcemia, especially in the younger population. Hypercalcemia persists after subtotal parathyroidectomy. It is important to diagnose this condition, not only in the index case but also in family members, because these patients should be advised against surgical intervention.