| [ Summary ] |
Our understanding of the molecular and biochemical bases of hypophosphatemic disorders is rapidly expanding. Studies of two types of inherited hypophosphatemic rickets, autosomal dominant hypophosphatemic rickets (ADHR), and X-linked hypohosphatemic rickets (XLH) have identified fibroblast growth factor 23 (FGF23) and PHEX, respectively, as the responsible genes for these disorders. ADHR is caused by missense mutations in the RXXR motif of FGF23, which prevents proteolytic inactivation. It is presumed that the increased full length active form of FGF23 results in the increased urinary loss of phosphate and hypophosphatemia in ADHR. The enzyme responsible for the cleavage of FGF23 has not been identified. PHEX encodes a endopeptidase, and one report has suggested that recombinant PHEX may cleave FGF23 at the RXXR motif. However, other studies have failed to confirm the cleavage of FGF23 by PHEX. Additional studies are necessary to determine how PHEX may regulate FGF23 action. |