Dr Econs has a patent pending for FGF23, and receives royalties from Kirin Brewery. All other authors state that they have no conflicts of interest.
FGF23 Concentrations Vary With Disease Status in Autosomal Dominant Hypophosphatemic Rickets†
Version of Record online: 16 JAN 2007
Copyright © 2007 ASBMR
Journal of Bone and Mineral Research
Volume 22, Issue 4, pages 520–526, April 2007
How to Cite
Imel, E. A., Hui, S. L. and Ecibs, M. J. (2007), FGF23 Concentrations Vary With Disease Status in Autosomal Dominant Hypophosphatemic Rickets. J Bone Miner Res, 22: 520–526. doi: 10.1359/jbmr.070107
- Issue online: 4 DEC 2009
- Version of Record online: 16 JAN 2007
- Manuscript Accepted: 10 JAN 2007
- Manuscript Revised: 11 DEC 2006
- Manuscript Received: 27 JUL 2006
- fibroblast growth factor 23;
- autosomal dominant hypophosphatemic rickets;
We measured FGF23 concentrations in subjects with ADHR. FGF23 and serum phosphate correlated positively in controls and negatively in subjects with ADHR. Elevated FGF23 concentrations were associated with lower phosphate values. The variable phenotype in ADHR may be caused by fluctuations in FGF23.
Introduction: Autosomal dominant hypophosphatemic rickets (ADHR) is a rare disorder of phosphaturia, hypophosphatemia, inappropriately low/normal calcitriol, and rickets/osteomalacia. ADHR is caused by mutations in a circulating peptide, fibroblast growth factor 23 (FGF23). We present the first report of FGF23 concentrations in subjects with ADHR. The aim was to test the hypotheses that subjects with ADHR have elevated FGF23 concentrations and that FGF23 concentrations are associated with disease severity.
Materials and Methods: This was an observational study at a tertiary referral center. Subjects were from three kindreds with FGF23 mutations causing ADHR (n = 42). Controls were participants from these families without mutations (n = 55). Fasting blood and urine samples were obtained. Biochemistries were determined, and FGF23 concentrations were measured using two ELISAs.
Results: Three cases are presented illustrating activity of disease and FGF23 concentrations. One case shows persistent hypophosphatemia and elevation of FGF23 concentrations, whereas another shows remission of hypophosphatemia corresponding to a decrease in previously elevated FGF23 concentrations. Overall cross-sectional group differences were nonsignificant for serum phosphate and FGF23 concentrations. C-terminal FGF23 concentration in controls was 61.0 ± 28.6 (SD) RU/ml (median, 52.5 RU/ml), and in subjects with mutations was 148.8 ± 374.5 RU/ml (median, 63.1 RU/ml). Mean intact FGF23 concentration in controls was 44.7 ± 14.9 pg/ml (median, 40.4 pg/ml), and in subjects with mutations was 83.2 ± 233.0 pg/ml (median, 39.0 pg/ml). C-terminal FGF23 concentrations were at least +2 SD in 10/42(24%), and intact FGF23 concentrations were at least +2 SD in 3/34(9%). Phosphate correlated positively with C-terminal and intact FGF23 in both controls and in subjects with mutations with phosphate >2.5 mg/dl but correlated significantly negatively with C-terminal and intact FGF23 in ADHR subjects with phosphate ≤2.5 mg/dl.
Conclusions: Elevated FGF23 concentrations are associated with hypophosphatemia in ADHR, and remission of the phenotype is associated with lower FGF23 concentrations. FGF23 has an opposite relationship with phosphate in ADHR compared with controls. We conclude that ADHR symptoms and disease severity likely fluctuate with FGF23 concentrations.