Endocrine Abstracts

Objective: To describe a novel mutation of the calcium sensing receptor gene (CaSR) in a family diagnosed with familial hypocalciuric hypercalcemia (FHH).

Case history: A 62 year old man being investigated for short term memory loss was referred to us by GP for hypercalcemia found on routine blood tests. He was asymptomatic otherwise. Repeat blood tests revealed serum calcium high at 2.88 mmol/l, inorganic phosphate of 0.75 mmol/l, and normal serum PTH of 2.9 pmol/l. Calcium creatinine clearance ratio performed on 24 hour urine collection of urine was 0.01 mmol/l. On the basis of these results, a diagnosis of FHH was entertained. Genetic testing revealed the patient to be heterozygous for P748L mutation in CaSR gene.

On our request, the patient’s daughter who was 36 weeks pregnant then agreed to be screened for this disorder and was found to be hypercalcemic. A healthy baby boy delivered by patient’s daughter had mild hypercalcemia as well. Genetic analysis of CaSR of both daughter and her son was found to be heterozygous for P748L mutation. As all the three members of the family showed same mutation in CaSR on gene analysis, we assume this mutation to be the likely cause for FHH in this family.

Conclusion: We describe a novel mutation in exon 7 of CaSR gene in a family with FHH. Identification of patients with FHH saves them from undergoing extensive investigations and parathyroidectomy. Continued identification and characterisation of naturally occurring CaSR mutations is critical to enhance our understanding of the workings of this important receptor.