Hypophosphatemia with elevations in serum fibroblast growth factor 23 in a child with Jansen's metaphyseal chondrodysplasia.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
University of Alabama School of Medicine, Department of Pediatric Endocrinology, Children's Park Place Suite 230, 1600 7th Avenue South, Birmingham, Alabama 35233, USA. dr.whitneyw.brown@erlanger.org
Whitney W
WW
Brown
Harald
H
Jüppner
Craig B
CB
Langman
Heather
H
Price
Emily G
EG
Farrow
Kenneth E
KE
White
Kenneth L
KL
McCormick
D002117:Calcitriol / Q000097:blood; D004392:Dwarfism / Q000097:blood*; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D017674:Hypophosphatemia / Q000097:blood*; D007223:Infant; D008297:Male; D010009:Osteochondrodysplasias / Q000097:blood*; D010281:Parathyroid Hormone / Q000097:blood / Q000502:physiology
C000717427:FGF23 protein, human; D010281:Parathyroid Hormone; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D002117:Calcitriol