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: Lisal J Folsom, Erik A Imel
• Journal: Current osteoporosis reports (Curr Osteoporos Rep) Vol. 13 Issue 2 Pg. 78-87 (Apr 2015) ISSN: 1544-2241 [Electronic] United States
• PMID: 25656441 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Diphosphonates
• FGF23 protein, human
• Phosphates
• Vitamin D
• Fibroblast Growth Factors
• 1,25-dihydroxyvitamin D
• Fibroblast Growth Factor-23
• N-Acetylgalactosaminyltransferases
• Glucuronidase
• Klotho Proteins

Topics

• Calcinosis (genetics, metabolism, therapy)
• Diet Therapy
• Diphosphonates (therapeutic use)
• Fibroblast Growth Factor-23
• Fibroblast Growth Factors (deficiency, genetics)
• Glucuronidase (genetics)
• Humans
• Hyperostosis, Cortical, Congenital (genetics, metabolism, therapy)
• Hyperphosphatemia (genetics, metabolism, therapy)
• Klotho Proteins
• Models, Genetic
• Mutation (genetics)
• N-Acetylgalactosaminyltransferases (genetics)
• Phosphates (metabolism)
• Vitamin D (analogs & derivatives, metabolism)
• Polypeptide N-acetylgalactosaminyltransferase