scholarly journals The Autosomal Dominant Hypophosphatemic Rickets R176Q Mutation in Fibroblast Growth Factor 23 Resists Proteolytic Cleavage and Enhancesin VivoBiological Potency

2003 ◽  
Vol 278 (11) ◽  
pp. 9843-9849 ◽  
Author(s):  
Xiu-Ying Bai ◽  
Dengshun Miao ◽  
David Goltzman ◽  
Andrew C. Karaplis
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Autosomal Dominant ◽  
Fibroblast Growth Factor 23 ◽  
Proteolytic Cleavage ◽  
Hypophosphatemic Rickets ◽  
Fibroblast Growth ◽  
Autosomal Dominant Hypophosphatemic Rickets

Fibroblast Growth Factor 23 (FGF23) and the kidney

2009 ◽  
Vol 32 (4) ◽  
pp. 232-239 ◽  
Author(s):  
George Tsagalis ◽  
Erasmia Psimenou ◽  
Efstathios Manios ◽  
Antonios Laggouranis
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Serum Phosphate ◽  
Phosphate Concentration ◽  
Hypophosphatemic Rickets ◽  
Fibroblast Growth ◽  
Autosomal Dominant Hypophosphatemic Rickets ◽  
Fgf 23

Phosphate homeostasis in humans is a complex phenomenon involving the interplay of several different organs and circulating hormones. Among the latter, parathyroid hormone (PTH), and vitamin D3 (Vit D3) were thought to be the main regulators of serum phosphate concentration since they mediated the intestinal, renal and bone responses that follow fluctuations in serum phosphate levels. The study of three rare disorders – tumor-induced osteomalacia (TIO), autosomal dominant hypophosphatemic rickets (ADHR) and X-linked hypophosphatemic rickets (XLH) – has offered a completely new insight into phosphate metabolism by unraveling the role of a group of peptides that can directly affect serum phosphate concentration by increasing urinary phosphate excretion. Fibroblast growth factor-23 (FGF-23) is the most extensively studied “phosphatonin”. The production, mechanism of action, effects in various target tissues, and its role in common clinical disorders are the focus of this review.

scholarly journals SAT-373 A Case of X Linked Hypophosphatemic Rickets Due to DE Novo Phex Gene Mutation

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Ahmed Badran ◽  
Renee Bargman
Keyword(s):  
Vitamin D ◽  
Growth Factor ◽  
Vitamin D Deficiency ◽  
Fibroblast Growth Factor ◽  
Gene Mutation ◽  
De Novo ◽  
Fibroblast Growth Factor 23 ◽  
Hypophosphatemic Rickets ◽  
Fibroblast Growth ◽  
Phex Gene

Abstract Introduction Rickets is a condition that can affect bones of infants and children. It is characterized by growth plate demineralization and can occur secondary to, most commonly, vitamin D deficiency or various problems with vitamin D, Calcium or Phosphate metabolism. Hypophosphatemic rickets (HR) is a type of rickets that is inherited by X linked dominant pattern mainly however it can be also inherited by autosomal dominant and recessive patterns in rare cases. X linked dominant type (XLH) affects about 1 in 20,000 newborns. Each of the other hereditary forms of HR has been identified in only a few families. Clinical features of XLH is similar to other types of rickets including metaphyseal widening, palpable rachitic rosaries, frontal prominence, malformation of the horizontal depression along the lower border of the chest, insufficient weight gain and leg bowing. Case presentation: A 10-month-old infant presented to endocrinology with vitamin D deficiency, low serum phosphorus and hyperparathyroidism. Physical examination showed macrocephaly with frontal bossing, widening of the wrists and rachitic rosaries. His lab results showed low 25 OH vitamin D (11 ng/ml) (N:20-50 ng/ml), low phosphorus (PO4) (3.3 mg/dl) (N:4-6.5 mg/dl), high PTH (113 pg/ml) (N: 20-65pg/ml), high alkaline phosphatase (ALP) (836 IU/L) (N: 135-518 IU/L) and normal calcium (Ca2+) (9.6 mg/dl) (N:9-11 mg/dl). Vitamin D treatment was started however his follow up lab results showed persistent hypophosphatemia for age (2.8mg/dl) and elevated ALP (600IU/l) despite normalization of vitamin D (38 ng/ml). Additional lab tests were done showing high PO4 excretion (19.5 mg/dl)(N:1:3.5 mg/dl), Ca/Cr ratio 0.005 (N <0.14), inappropriately normal FGF23 level (129 RU/ml) (N: >124 RU/mL). Genetic testing showed de novo mutation in PHEX gene (871C>T) which is consistent with XLH. PHEX gene mutation is the most common mutation associated with XLH. Normally this gene can directly or indirectly regulate a protein called fibroblast growth factor 23 (produced from FGF23 gene). This protein normally inhibits renal reabsorption of phosphate into the bloodstream. Gene mutations increase the production or reduce the breakdown of fibroblast growth factor 23 leading to an overactivation of this protein and reduction of phosphate reabsorption by the kidneys, resulting in hypophosphatemia. The patient was maintained on Burosomab (0.4 mg/kg biweekly); a recombinant human monoclonal antibody (IgG1) that binds to and inhibits the activity of fibroblast growth factor 23 (FGF23) and increases the phosphate reabsorption in the renal tubules. Conclusion: XLH due to PHEX gene mutation should be considered in rachitic children who have persistently low phosphate levels despite treating vitamin D deficiency.

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