A Novel Genetic Variant Resulting in Familial Hypocalciuric Hypercalcaemia

Presentation A 17-year-old male was referred to the endocrinology service with an incidental finding of hypercalcaemia. Over the course of the previous year his calcium ranged from 2.64-2.77mmol/L (reference range: 2.2-2.6mmol/L) in the setting of a normal/low parathyroid hormone (PTH) of 14-35pg/ml (reference range: 15-65pg/ml). Diagnosis Following biochemical confirmation of hypocalciuric hypercalcaemia he was referred for molecular genetic analysis which showed a heterozygous variant in the CASR gene previously undescribed in the literature: c.491A>G; p.GIn164Arg. Treatment The patient and his parents were reassured with regard to the benign nature of the condition and counselled with regard to its inheritance. Discussion Though there is little data on this genetic variant, it is assumed to have caused familial hypocalciuric hypercalcaemia (FHH) in this gentleman. FHH is an important differential in hypercalcaemia as it can be misdiagnosed as primary hyperparathyroidism, potentially leading to unnecessary surgical intervention.