Significantly elevated calcium levels and gallstone disease in a patient with familial hypocalciuric hypercalcaemia.

Abstract

Summary: Familial hypocalciuric hypercalcaemia (FHH) is a rare, benign genetic disorder of calcium homeostasis caused by inactivating variants in CaSR, GNA11, or AP2S1 genes. It is typically characterised by mild, asymptomatic hypercalcaemia and low urinary calcium excretion. Differentiation from primary hyperparathyroidism (PHPT) is essential, as misdiagnosis can lead to unnecessary surgery. We report a case of FHH type 1 (FHH1) in a man in his thirties presenting with a serum calcium level of 2.97 mmol/L, which is at the severe end of the FHH spectrum. Genetic testing revealed a heterozygous CaSR nonsense variant (NM_000388.4:c.1942C>T, p.Arg648Ter) consistent with FHH1. The patient had clinically stable hypercalcaemia, which was not treated. During follow-up, he developed gallstones treated with a laparoscopic cholecystectomy. A review of the literature demonstrated that calcium levels approaching 3 mmol/L, although uncommon, have been reported in other cases of FHH1. We review the literature regarding a potential association between FHH and gallstones. This case highlights that FHH can present with relatively marked hypercalcaemia, reinforcing the need for genetic evaluation before surgery, and suggests a possible but under-explored relationship between FHH and gallstone disease.

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