CONTEXT: Previous studies have suggested a regulatory relationship between serum phosphorus, vitamin D, and fibroblast growth factor 23 (FGF23), a hormone that promotes renal excretion of phosphate. Despite these associations, the identity of the primary regulator of serum FGF23 is unresolved. Jansen's metaphyseal chondrodysplasia is a rare autosomal dominant disorder associated with short-limbed dwarfism and other characteristic skeletal abnormalities. This condition is caused by mutations in the PTH/PTHrP receptor that result in ligand-independent cAMP accumulation, thus rendering the receptor constitutively active. These patients typically exhibit asymptomatic hypercalcemia and hypophosphatemia despite low or undetectable serum levels of PTH and PTHrP. EVIDENCE ACQUISITION: A literature search revealed that serum FGF23 levels had not been studied in patients with Jansen's syndrome, a disorder in which the biochemical features present a unique opportunity to study the possible relationship between FGF23 and calcium-phosphorus-vitamin D metabolism. A case of Jansen's syndrome is presented in which serum FGF23 concentrations, along with serum phosphorus and 1,25(OH)(2) vitamin D levels, were measured and compared with those of age-matched controls. EVIDENCE SYNTHESIS: Serum FGF23 concentrations in the patient with Jansen's syndrome were found to be markedly and persistently elevated, compared with values in healthy, age-matched controls, despite hypophosphatemia and normal 1,25(OH)(2) vitamin D levels. CONCLUSION: Together, our findings indicate that serum FGF23 could be governed by factor(s) other than serum phosphorus, potentially by activation of the PTH/PTHrP receptor in bone.
CONTEXT: Previous studies have suggested a regulatory relationship between serum phosphorus, vitamin D, and fibroblast growth factor 23 (FGF23), a hormone that promotes renal excretion of phosphate. Despite these associations, the identity of the primary regulator of serum FGF23 is unresolved. Jansen's metaphyseal chondrodysplasia is a rare autosomal dominant disorder associated with short-limbed dwarfism and other characteristic skeletal abnormalities. This condition is caused by mutations in the PTH/PTHrP receptor that result in ligand-independent cAMP accumulation, thus rendering the receptor constitutively active. These patients typically exhibit asymptomatic hypercalcemia and hypophosphatemia despite low or undetectable serum levels of PTH and PTHrP. EVIDENCE ACQUISITION: A literature search revealed that serum FGF23 levels had not been studied in patients with Jansen's syndrome, a disorder in which the biochemical features present a unique opportunity to study the possible relationship between FGF23 and calcium-phosphorus-vitamin D metabolism. A case of Jansen's syndrome is presented in which serum FGF23 concentrations, along with serum phosphorus and 1,25(OH)(2) vitamin D levels, were measured and compared with those of age-matched controls. EVIDENCE SYNTHESIS: Serum FGF23 concentrations in the patient with Jansen's syndrome were found to be markedly and persistently elevated, compared with values in healthy, age-matched controls, despite hypophosphatemia and normal 1,25(OH)(2) vitamin D levels. CONCLUSION: Together, our findings indicate that serum FGF23 could be governed by factor(s) other than serum phosphorus, potentially by activation of the PTH/PTHrP receptor in bone.
Authors: Tobias Larsson; Xijie Yu; Siobhan I Davis; Mohamad S Draman; Sean D Mooney; Michael J Cullen; Kenneth E White Journal: J Clin Endocrinol Metab Date: 2005-02-01 Impact factor: 5.958
Authors: Michael T Collins; John R Lindsay; Alka Jain; Marilyn H Kelly; Carolee M Cutler; Lee S Weinstein; Jie Liu; Neal S Fedarko; Karen K Winer Journal: J Bone Miner Res Date: 2005-07-18 Impact factor: 6.741
Authors: Sergei A Kuznetsov; Mara Riminucci; Navid Ziran; Takeo W Tsutsui; Alessandro Corsi; Laura Calvi; Henry M Kronenberg; Ernestina Schipani; Pamela Gehron Robey; Paolo Bianco Journal: J Cell Biol Date: 2004-12-20 Impact factor: 10.539
Authors: Mara Riminucci; Michael T Collins; Neal S Fedarko; Natasha Cherman; Alessandro Corsi; Kenneth E White; Steven Waguespack; Anurag Gupta; Tamara Hannon; Michael J Econs; Paolo Bianco; Pamela Gehron Robey Journal: J Clin Invest Date: 2003-09 Impact factor: 14.808