Endocrine Abstracts

Introduction: Familial hypocalciuric hypercalcemia (FHH) is a rare mostly asymptomatic genetic disorder affecting the calcium sensing receptor (CaSR) and its associated proteins with autosomal dominant inheritance. Mutation in AP2S1 gene is responsible for FHH3.

Aim: Expand the phenotype of FHH type 3.

Methods: Clinical and biochemical characterization of a patient with de-novo FHH3 mutation.

Results: S.Z, A 30-year-old man was hospitalized for recurrent pancreatitis. His medical history included chronic hypercalcemia in the range of 11.7–13.3 mg/dl attributed to his prior clinical diagnosis of FHH. Abdominal imaging and lipid profile were unremarkable. The working diagnosis was of hypercalcemia-related acute pancreatitis. He was treated conservatively with resolution of symptoms and normalization of serum amylase and lipase. A multi-gene panel that was performed (INVITAE) revealed a heterozygous mutation in the AP2S1 gene-p.Arg15Leu. His parents and two siblings were normocalcemic. A second genetic panel for pancreatitis related genes was negative. DXA bone mineral density revealed Z score of −2.3 at LS and −2.9 at FN and TH – a typical finding in FHH3 patients. Cinacalcet at a dose of 120 mg daily was well tolerated and normalized calcium levels with no episodes of pancreatitis within 26 months of follow-up. His three-year-old son is followed for speech delay and was found to be hypercalcemic; he carries the same AP2S1 mutation.

Conclusions: We describe a family with a de novo mutation in the AP2S1 gene presenting with recurrent pancreatitis, low bone mass and speech delay thus expanding the phenotype of FHH3.