A novel CASR variant in a family with familial hypocalciuric hypercalcaemia and primary hyperparathyroidism.

SUMMARY: Familial hypocalciuric hypercalcaemia (FHH) is a dominantly inherited, lifelong benign disorder characterised by asymptomatic hypercalcaemia, relative hypocalciuria and variable parathyroid hormone levels. It is caused by loss-of-function pathogenic variants in the calcium-sensing receptor (CASR) gene. Primary hyperparathyroidism (PHPT) is characterised by variable hypercalcaemia in the context of non-suppressed parathyroid hormone levels. Unlike patients with FHH, patients with severe hypercalcaemia due to PHPT are usually symptomatic and are at risk of end-organ damage affecting the kidneys, bone, heart, gastrointestinal system and CNS. Surgical resection of the offending parathyroid gland(s) is the treatment of choice for PHPT, while dietary adjustment and reassurance is the mainstay of management for patients with FHH. The occurrence of both FHH and primary hyperparathyroidism (PHPT) in the same patient has been described. We report an interesting case of FHH due to a novel CASR variant confirmed in a mother and her two daughters and the possible coexistence of FHH and PHPT in the mother, highlighting the challenges involved in diagnosis and management. LEARNING POINTS: Familial hypocalciuric hypercalcaemia (FHH) and primary hyperparathyroidism (PHPT) can coexist in the same patient. Urinary calcium creatinine clearance ratio can play a role in distinguishing between PHPT and FHH. Genetic testing should be considered in managing patients with PHPT and FHH where the benefit may extend to the wider family. Family segregation studies can play an important role in the reclassification of variants of uncertain significance. Parathyroidectomy has no benefit in patients with FHH and therefore, it is important to exclude FHH prior to considering surgery. For patients with coexisting FHH and PHPT, parathyroidectomy will reduce the risk of complications from the severe hypercalcaemia associated with PHPT.

Rapid genetic testing for Gaucher disease by reverse hybridization.

BACKGROUND: We evaluated a reverse hybridization method for the simultaneous detection of nine mutations that are associated with Gaucher disease. RESULTS AND CONCLUSION: Results were in agreement with those obtained by a polymerase chain reaction-restriction digestion method. The hybridization method produced results more quickly and with less operator input.