Expanding the phenotype of familial hypocalciuric hypercalcemia type 3: Case report and review of the literature

Background: Familial hypocalciuric hypercalcemia (FHH) is a rare condition that affects the calcium sensing receptor and its associated proteins, causing parathyroid hormone (PTH)-mediated hypercalcemia. FHH is inherited in an autosomal dominant pattern. Most persons with FHH are asymptomatic. Case presentation: A 30-year-old Caucasian male was sent for evaluation to our endocrinology unit due to recurrent pancreatitis in the context of chronic hypercalcemia, and a biochemical profile compatible with FHH. Genetic evaluation did not show any mutations associated with pancreatitis but revealed a known heterozygous variant in the AP2S1 gene: c.44G > T, p.Arg15Leu, responsible for FHH type 3 (FHH3). A bone mineral density DXA scan detected low bone mass, in the osteoporotic range, with no other secondary causes. Both his parents were normocalcemic. Treatment with the calcimimetic cinacalcet normalized his blood calcium; no episodes of pancreatitis have occurred during 26 months follow up. The patient's only child was found to have hypercalcemia at age three years. His lab results were compatible with the diagnosis of FHH, and he was found to carry the same AP2S1 gene mutation as his father. His calcium level was elevated but he did not have any symptoms related to hypercalcemia. He was diagnosed with speech delay. Conclusions: We describe a man with a de-novo mutation leading to FHH3, who presented with a rare combination of symptoms, including recurrent pancreatitis and low bone mass, whereas his child presented with speech delay. Hypercalcemia and related FHH3 morbidities may respond to calcimimetics.