title: Iron and fibroblast growth factor 23 in X-linked hypophosphatemia.
abstract: BACKGROUND
  Excess fibroblast growth factor 23 (FGF23) causes hypophosphatemia in autosomal dominant hypophosphatemic rickets (ADHR) and X-linked hypophosphatemia (XLH). Iron status influences C-terminal FGF23 (incorporating fragments plus intact FGF23) in ADHR and healthy subjects, and intact FGF23 in ADHR. We hypothesized that in XLH serum iron would inversely correlate to C-terminal FGF23, but not to intact FGF23, mirroring the relationships in normal controls.
  
  
  METHODS
  Subjects included 25 untreated outpatients with XLH at a tertiary medical center and 158 healthy adult controls. Serum iron and plasma intact FGF23 and C-terminal FGF23 were measured in stored samples.
  
  
  RESULTS
  Intact FGF23 was greater than the control mean in 100% of XLH patients, and >2SD above the control mean in 88%, compared to 71% and 21% respectively for C-terminal FGF23. In XLH, iron correlated negatively to log-C-terminal FGF23 (r=-0.523, p<0.01), with a steeper slope than in controls (p<0.001). Iron was not related to log-intact FGF23 in either group. The log-ratio of intact FGF23 to C-terminal FGF23 was higher in XLH (0.00±0.44) than controls (-0.28±0.21, p<0.01), and correlated positively to serum iron (controls r=0.276, p<0.001; XLH r=0.428, p<0.05), with a steeper slope in XLH (p<0.01).
  
  
  CONCLUSIONS
  Like controls, serum iron in XLH is inversely related to C-terminal FGF23 but not intact FGF23. XLH patients are more likely to have elevated intact FGF23 than C-terminal FGF23. The relationships of iron to FGF23 in XLH suggest that altered regulation of FGF23 cleaving may contribute to maintaining hypophosphatemia around an abnormal set-point.
authors: Indiana University School of Medicine, Department of Medicine, USA; Indiana University School of Medicine, Department of Pediatrics, USA. Electronic address: eimel@iupui.edu.
authors: Erik A
authors: EA
authors: Imel
authors: Indiana University School of Medicine, Department of Medicine, USA.
authors: Amie K
authors: AK
authors: Gray
authors: Indiana University School of Medicine, Department of Medicine, USA.
authors: Leah R
authors: LR
authors: Padgett
authors: Indiana University School of Medicine, Department of Medicine, USA.
authors: Michael J
authors: MJ
authors: Econs
mesh_terms: D000328:Adult; D001681:Biological Assay; D016022:Case-Control Studies; D053098:Familial Hypophosphatemic Rickets / Q000097:blood*; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D007501:Iron / Q000097:blood*; D008297:Male; D012015:Reference Standards; D055815:Young Adult
chemical_list: C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D007501:Iron
keywords: FGF23; Fibroblast growth factor 23; Iron; Phosphate; X-linked hypophosphatemia