Pathogenesis of FGF23-Related Hypophosphatemic Diseases Including X-linked Hypophosphatemia

Since phosphate is indispensable for skeletal mineralization, chronic hypophosphatemia causes rickets and osteomalacia. Fibroblast growth factor 23 (FGF23), which mainly produced by osteocytes in bone, functions as the central regulator of metabolism increasing renal excretion suppressing production 1,25-dihydroxyvitamin D. The excessive action FGF23 results hypophosphatemic diseases, include a number genetic disorders such X-linked (XLH) tumor-induced osteomalacia (TIO). Phosphate-regulating gene homologous to endopeptidase on X chromosome (PHEX), dentin matrix protein 1 (DMP1), ectonucleotide pyrophosphatase phosphodiesterase-1, family with sequence similarity 20c, inactivating variants are responsible FGF23-related hereditary rickets/osteomalacia, highly expressed osteocytes, similar FGF23, suggesting that they local negative regulators FGF23. Autosomal dominant (ADHR) caused cleavage-resistant iron deficiency increases serum levels manifestation symptoms ADHR. Enhanced FGF receptor (FGFR) signaling suggested be involved overproduction XLH autosomal recessive type 1, inactivation PHEX DMP1, respectively. TIO phosphaturic tumors, often positive FGFR. may also associated McCune-Albright syndrome, linear sebaceous nevus intravenous administration iron. This review summarizes current knowledge pathogenesis diseases.