Mutational analysis of a patient with familial hypocalciuric hypercalcaemia identifies a novel p. Ser182Cys mutation, which is predicted to disrupt the calcium sensing receptor …

Familial hypocalciuric hypercalcaemia (FHH) is an inherited disorder of calcium homeostasis, which is caused by germline loss-of-function mutations of the calcium-sensing receptor (CaSR) in 70% of cases. We report a 22 year old woman who was referred with asymptomatic hypercalcaemia. Biochemical investigations revealed hypercalcaemia on 3 of 4 occasions with adjusted serum calcium ranging from 2.59–2.80 mmol/l (normal range 2.20–2.60 mmol/l). Parathyroid hormone levels ranged from 4.2–6.5 pmol/l (normal range 1.6–7.2 pmol/l). Urinary calcium excretion was 3.5 mmol in 24 hours (normal range 2.5–7.5 mmol/24 h). Spot urinary calcium creatinine clearance ratio was calculated at 0.0095 (normal> 0.01). Investigations were consistent with a diagnosis of FHH, prompting genetic testing. Molecular analysis of the CaSR gene revealed a novel heterozygous single base pair substitution, Cytosine to …