title: Hypophosphatemic rickets: lessons from disrupted FGF23 control of phosphorus homeostasis.
abstract: Fibroblast growth factor-23 (FGF23) regulates phosphate reabsorption in the kidney and therefore plays an essential role in phosphate balance in humans. There is a host of defects that ultimately lead to excess FGF23 levels and thereby cause renal phosphate wasting and hypophosphatemic rickets. We describe the genetic, pathophysiologic, and clinical aspects of this group of disorders with a focus on X-linked hypophosphatemia (XLH), the best characterized of these abnormalities. We also discuss autosomal dominant hypophosphatemic rickets (ADHR), autosomal recessive hypophosphatemic rickets (ARHR) and tumor-induced osteomalacia (TIO) in addition to other rarer FGF23-mediated conditions. We contrast the FGF23-mediated disorders with FGF23-independent hypophosphatemia, specifically hypophosphatemic rickets with hypercalciuria (HHRH). Errant diagnosis of hypophosphatemic disorders is common. This review aims to enhance the recognition and appropriate diagnosis of hypophosphatemia and to guide appropriate treatment.
authors.affiliation: Department of Pediatrics (Endocrinology), Yale University School of Medicine, 333 Cedar Street, PO Box 208064, New Haven, CT, 06520, USA, Bracha.goldsweig@yale.edu.
authors.forename: Bracha K
authors.initials: BK
authors.lastname: Goldsweig
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Carpenter
mesh_terms: D001842:Bone and Bones / Q000378:metabolism; D002116:Calcitonin / Q000627:therapeutic use; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D010018:Osteomalacia / Q000503:physiopathology; D010758:Phosphorus / Q000378:metabolism*; D063730:Rickets, Hypophosphatemic / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology*
chemical_list: C000717427:FGF23 protein, human; D010758:Phosphorus; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D002116:Calcitonin