title: Hyperphosphatemic familial tumoral calcinosis: genetic models of deficient FGF23 action.
abstract: Hyperphosphatemic familial tumoral calcinosis (hFTC) is a rare disorder of phosphate metabolism defined by hyperphosphatemia and ectopic calcifications in various locations. To date, recessive mutations have been described in three genes involving phosphate metabolism: FGF23, GALNT3, and α-Klotho, all of which result in the phenotypic presentation of hFTC. These mutations result in either inadequate intact fibroblast growth factor-23 (FGF23) secretion (FGF23 or GALNT3) or resistance to FGF23 activity at the fibroblast growth factor receptor/α-Klotho complex (α-Klotho). The biochemical consequence of limitations in FGF23 activity includes increased renal tubular reabsorption of phosphate, hyperphosphatemia, and increased production of 1,25-dihydroxyvitamin D. The resultant ectopic calcifications can be painful and debilitating. Medical treatments are targeted toward decreasing intestinal phosphate absorption or increasing phosphate excretion; however, results have been variable and generally limited. Treatments that would increase FGF23 levels or signaling would more appropriately target the genetic etiologies of this disease and perhaps be more effective.
authors: Department of Medicine, Division of Endocrinology, Indiana University School of Medicine, 1120 W. Michigan Street, Gatch Clinical Building Room 459, Indianapolis, IN, 46202, USA, FolsomL@iupui.edu.
authors: Lisal J
authors: LJ
authors: Folsom
authors: Erik A
authors: EA
authors: Imel
mesh_terms: D002114:Calcinosis / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D004035:Diet Therapy; D004164:Diphosphonates / Q000627:therapeutic use; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000172:deficiency* / Q000235:genetics*; D005966:Glucuronidase / Q000235:genetics; D006801:Humans; D006958:Hyperostosis, Cortical, Congenital / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D054559:Hyperphosphatemia / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D000090265:Klotho Proteins; D008957:Models, Genetic; D009154:Mutation / Q000235:genetics*; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics; D010710:Phosphates / Q000378:metabolism; D014807:Vitamin D / Q000031:analogs & derivatives / Q000378:metabolism; D000097763:Polypeptide N-acetylgalactosaminyltransferase
chemical_list: D004164:Diphosphonates; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors; D005966:Glucuronidase; D000090265:Klotho Proteins; D017350:N-Acetylgalactosaminyltransferases; D010710:Phosphates; D014807:Vitamin D; D000097763:Polypeptide N-acetylgalactosaminyltransferase; C000717427:FGF23 protein, human; C097949:1,25-dihydroxyvitamin D
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