Familial Hypocalciuric Hypercalcemia - Current Diagnostics and Therapy

Familial hypocalciuric hypercalcemia (FHH) is an autosomal dominant inherited disease with inactivating mutations in the calcium-sensing receptor (CaSR) and lifelong high penetrance for mild hypercalcemia and relative hypocalciuria. Parathyroid hormone is inappropriate high for the elevated calcium, which reflects parathyroid resistance. The phenotype is mainly asymptomatic, kidney stones occur rarely. The diagnostic key in FHH is the low calcium/creatinine clearance below 0.01. Patients with FHH are potentially misdiagnosed as having asymptomatic primary hyperparathyroidism (pHpt) and may have parathyroidectomy, which does not correct the hypercalcemia. Molecular genetic analysis of the CaSR offers a valuable supplement to the differential diagnosis of pHpt. The rare and life-threatening syndrome of neonatal severe hyperparathyroidism (NSHPT) with severe hypercalcemia is usually caused by homozygous mutations of the CaSR and has to be treated by urgent total parathyroidectomy.