Genetics of primary hypercalciuria

Primary hypercalciuria is a highly heterogeneous complex metabolic disorder and it can be schematically represented by three general distinct clinical entities, such as absorptive hypercalciuria, renal hypercalciuria and resorptive hypercal- ciuria. In fact, other than absorptive hypercalciuria, hypercal-ciuria has been described in several monogenic syndromes such as Dent’s disease, Bartter’s Syndrome, Hereditary Hy-pomagnesaemia- ypercalciuria Syndrome, hypercalciuric syndromes due to mutations of calcium sensing receptor gene such as Familial Hypocalcaemia with Hypercalciuria Syndrome and Familial Hypercalcemia and Hypercalciuria Syndrome and in a less common forms of hypophos-phatemia with hypercalciuria. Of course, environmental fac-tors influence hypercalciuria, but a strong genetic compo- nent has been clearly demonstrated. In fact, in many hyper-lciuric conditions a familial trait has been observed indi-cating the existence of inherited predisposing gene muta-tions. Forty to 45% of patients with idiopathic hypercalciuria exhibit at least one family member with nephrolithiasis. An apparent autosomal inheritance of hypercalciuria has been reported as also a clear autosomal recessive transmission in individual kindreds. Up to date, several genetic defects have been already identified accounting for familial hypercalci-uria, but others are still waiting for being unraveled. Howev-er, the genes responsible for inherited hypercalciuria might also account for sporadic form, as reported in literature, in-cluding isolated or incidental hypercalciuria. Here we will briefly review the more recent evidences accumulated in the international literature in this fascinating field of human a t h o p h y s i o