In addition either activating or inactivating mutations of the calcium-sensing receptor gene lead either to hypocalcemic hypercalciuria or hypercalcemic hypocalciuria.
FHH is typically caused by a heterozygous inactivating mutation of the calcium-sensing receptor (CaSR) and characterized by moderate hypercalcemia, inappropriately normal or elevated serum parathyroid hormone (PTH), and relative hypocalciuria (Fe<sub>Ca</sub> < 2%) with histologically normal parathyroid glands.
Conclusions Patients with CASR mutations may not fit the classic clinical pictures of hypercalcemia with hypocalciuria or hypocalcemia with hypercalciuria.
Consequently, patients with HNF1β mutations may have reduced CaSR activity in the kidney, which could explain cyst progression and hyperabsorption of Ca<sup>2+</sup> and Mg<sup>2+</sup> in the TAL resulting in hypocalciuria.
FHH is caused by inactivating mutations in the calcium sensing receptor (CASR) gene leading to a general calcium-hyposensitivity, compensatory hypercalcaemia and hypocalciuria.
A novel inactivating mutation (Q459R) was identified in exon 4 of both alleles of the CASR in the proband, who presented with asymptomatic hypercalcemia and hypocalciuria at age 2 yr.
However, one adult patient with severe hypercalcaemia and hypocalciuria has been reported to have a homozygous inactivating mutation in CaSR (Pro39Ala).