title: Fibroblast growth factor-23 and renin-angiotensin system levels in vitamin-D-dependent rickets type I.
abstract: As 1,25(OH)2D3 vitamin D3 induces fibroblast growth factor-23 (FGF-23) production and suppresses the renin-angiotensin-aldosterone system (RAAS), its absence in vitamin-D-dependent rickets type I (VDDR-I) may have adverse health consequences.
  
  
  
  An infant presented at age 8 months with hypocalcemia and rickets and very low 1,25(OH)2D3 levels. Genetic analysis confirmed VDRR-I, and calcitriol therapy was initiated. During periods of nonadherence to therapy, chemical measurements revealed detectable FGF-23 levels, with undetectable 1,25(OH)2D3, hypophosphatemia, low tubular reabsorption of phosphate, hypocalcemia, and very elevated parathyroid hormone (PTH) levels. These changes, in addition to elevated RAAS levels, normalized during calcitriol therapy despite elevated FGF-23 levels. At age 12 years, all rachitic manifestations were absent, and bone mineral density (BMD) and the echocardiogram were normal.
  
  
  
  Whereas 1,25(OH)2D3 is not indispensable for FGF-23 production, PTH in the absence of vitamin D may maintain FGF-23 secretion despite hypocalcemia. Normalization of urinary phosphate losses despite elevated FGF-23 during calcitriol-mediated suppression of secondary hyperparathyroidism points to a cardinal role of PTH as a cause of the phosphaturia in VDRR-I. Normalization of RAAS by calcitriol may conceivably prevent adverse cardiovascular outcomes.
authors.affiliation: Division of Pediatric Nephrology, University of Miami Miller School of Medicine, PO Box 016960(M-714), Miami, FL, 33101, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Cuervo
authors.affiliation: Division of Pediatric Nephrology, University of Miami Miller School of Medicine, PO Box 016960(M-714), Miami, FL, 33101, USA.
authors.forename: Carolyn L
authors.initials: CL
authors.lastname: Abitbol
authors.affiliation: Division of Pediatric Nephrology, University of Miami Miller School of Medicine, PO Box 016960(M-714), Miami, FL, 33101, USA.
authors.forename: Gaston E
authors.initials: GE
authors.lastname: Zilleruelo
authors.affiliation: Division of Pediatric Nephrology, University of Miami Miller School of Medicine, PO Box 016960(M-714), Miami, FL, 33101, USA. mfreundlich@med.miami.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Freundlich
mesh_terms: D002117:Calcitriol / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D053098:Familial Hypophosphatemic Rickets / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D007223:Infant; D012084:Renin-Angiotensin System / Q000502:physiology*; D014815:Vitamins / Q000627:therapeutic use
chemical_list: C000717427:FGF23 protein, human; D014815:Vitamins; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D002117:Calcitriol
keywords: Activated vitamin D; Children; FGF-23; PTH; RAAS; Rickets