Heritable and acquired disorders of phosphate metabolism: Etiologies involving FGF23 and current therapeutics.
Phosphate is critical for many cellular processes and structural functions, including as a key molecule for nucleic acid synthesis and energy metabolism, as well as hydroxyapatite formation in bone. Therefore it is critical to maintain tight regulation of systemic phosphate levels. Based upon its broad biological importance, disruption of normal phosphate homeostasis has detrimental effects on skeletal integrity and overall health. Investigating heritable diseases of altered phosphate metabolism has led to key discoveries underlying the regulation and systemic actions of the phosphaturic hormone Fibroblast growth factor-23 (FGF23). Both molecular and clinical studies have revealed novel targets for the development and optimization of therapies for disorders of phosphate handling. This review will focus upon the bridge between genetic discoveries involving disorders of altered FGF23 bioactivity, as well as describe how these findings have translated into pharmacologic application.
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
Erica L
EL
Clinkenbeard
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA. Electronic address: kenewhit@iupui.edu.
Kenneth E
KE
White
D000818:Animals; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D023281:Genomics; D006801:Humans; D017674:Hypophosphatemia / Q000235:genetics*; D040582:Inheritance Patterns / Q000235:genetics*; D010710:Phosphates / Q000378:metabolism*
C000717427:FGF23 protein, human; D010710:Phosphates; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23
FGF-23; Genetics; Hyperphosphatemia; Hypophosphatemia; Klotho; Tumoral calcinosis