Endocrine Abstracts

Introduction

Familial hypocalciuric hypercalcemia (FHH) is an autosomal dominant trait comprising hypercalcemia, hypophosphatemia and an unusually low renal clearance of calcium. The vast majority of FHH is caused by loss-of-function mutations in the gene CASR, which codes for the calcium-sensing receptor (CASR). CASR is a G-protein coupled membrane receptor expressed in the parathyroid glands and the kidneys, among other tissues. It is generally asymptomatic and does not require treatment. Genetic testing for FHH-associated mutations in CASR can help to prevent unnecessary and inappropriate parathyroidectomy in patients with FHH.

Case: A 41-year-old male presented with an elevated serum calcium on routine testing. A non – tourniqued, corrected serum calcium taken showed a reading of 2.91 mmol/l, which remained elevated on repeated testing. He had no past medical history and did not take any regular medications. No symptoms of hypercalcaemia were present. There was no family history of note. Physical examination was unremarkable.

The remainder of his blood work showed a normal serum creatinine, ACE concentration, TFTs and serum protein electrophoresis. His parathyroid hormone was 58 pg/ml (reference range 10 – 65 pg/ml). A urinary calcium/creatinine ratio was abnormally low at 0.002.

Our patient subsequently underwent CASR gene testing. He was found to have a C to T nucleotide substitution in exon 7 of CASR gene (c.2254C>T), p.Arg752Cys (Arginine replaced with cysteine). This mutation has not been described previously.

Discussion: Given the biochemical findings it is likely this is an inactivating mutation causing FHH. The patient’s mother and brother had normal serum calcium levels and were negative for CASR mutation. Unfortunately his father had died. We speculate that this is a de novo mutation causing FHH.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.