Renal phosphate wasting disorders: clinical features and pathogenesis.
Rickets and osteomalacia are associated with hypophosphatemia in several disease states, including X-linked hypophosphatemic rickets, autosomal-dominant hypophosphatemic rickets, and tumor-induced osteomalacia. Recent advances in the understanding of these diseases include discovery of mutations in the genes encoding human phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX) and fibroblast growth factor 23 (FGF-23) and the finding of overproduction of FGF-23 and other proteins including matrix extracellular phosphoglycoprotein (MEPE) and frizzled-related protein 4 (FRP-4) in tumor-induced osteomalacia. Research is ongoing to better define how these proteins relate to each other and to the sodium-phosphate cotransporter in both normal and abnormal phosphate metabolism. New and improved therapies for disorders of phosphate metabolism, osteomalacia, and rickets will develop as our knowledge of phosphate metabolism grows.
Brame
Lori A
LA
Department os Medicine, Indiana University School of Medicine, Indiana, IN 46202, USA.
White
Kenneth E
KE
Econs
Michael J
MJ
D002117:Calcitriol / Q000627:therapeutic use; D004195:Disease Models, Animal; D000089703:Fibroblast Growth Factor-23; D040181:Genetic Diseases, X-Linked; D006801:Humans; D010018:Osteomalacia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D053402:PHEX Phosphate Regulating Neutral Endopeptidase; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012279:Rickets / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters / Q000378:metabolism*
C000717427:FGF23 protein, human; D011506:Proteins; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters; D000089703:Fibroblast Growth Factor-23; D053402:PHEX Phosphate Regulating Neutral Endopeptidase; C506231:PHEX protein, human; D002117:Calcitriol