Description of 5 Novel SLC34A3/NPT2c Mutations Causing Hereditary Hypophosphatemic Rickets With Hypercalciuria

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare autosomal-recessive disorder. The disease was mapped to SLC34A3, the gene encoding renal sodium-phosphate (Pi) cotransporter NPT2c.1 Hypophosphatemia leads to suppression of fibroblast growth factor 23 (FGF23), increased 1,25-dihydroxy vitamin D (1,25(OH)2D), and hypercalciuria, the hallmark of HHRH, which is shared by a group of Pi wasting disorders caused by loss-of-function mutations in SLC34A1/NPT2a2 but differentiates it from X-linked and autosomal forms of FGF23-dependent hypophosphatemia.