In addition either activating or inactivating mutations of the calcium-sensing receptor gene lead either to hypocalcemic hypercalciuria or hypercalcemic hypocalciuria.
However, one adult patient with severe hypercalcaemia and hypocalciuria has been reported to have a homozygous inactivating mutation in CaSR (Pro39Ala).
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.
FHH is caused by inactivating mutations in the calcium sensing receptor (CASR) gene leading to a general calcium-hyposensitivity, compensatory hypercalcaemia and hypocalciuria.
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.
Conclusions Patients with CASR mutations may not fit the classic clinical pictures of hypercalcemia with hypocalciuria or hypocalcemia with hypercalciuria.
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.