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Metabolism. 2020 Feb;103S:153865. doi: 10.1016/j.metabol.2019.01.006. Epub 2019 Jan 19.

Physiology of FGF23 and overview of genetic diseases associated with renal phosphate wasting.

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Reference Center for Rare Renal Disorders, Reference Center for Rare Disorders of Calcium and Phosphate Metabolism, Department of Pediatric Nephrology, Rheumatology and Dermatology, Femme Mère Enfant Hospital, Bron Cedex, France; Lyon-Est Medical School, Lyon 1 University, Lyon, France; INSERM 1033, LYOS, Bone Disorders Prevention, Lyon, France. Electronic address:
Paris Descartes University, EA2496, Faculty of Dental Surgery, Montrouge, France.
Paris Descartes University of Medicine, Necker-Enfants Malades Institute, INSERM U1151, France; Functional Exploration Department, Necker-Enfants Malades Hospital, AP-HP, Paris, France.


Phosphate is a cornerstone of several physiological pathways including skeletal development, bone mineralization, membrane composition, nucleotide structure, maintenance of plasma pH, and cellular signaling. The kidneys have a key role in phosphate homeostasis with three hormones having important functions in renal phosphate handling or intestinal absorption: parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), and 1-25-dihydroxyvitamin D (1,25(OH)2D). FGF23 is mainly synthesized by osteocytes; it is a direct phosphaturic factor that also inhibits 1,25(OH)2D and PTH. In addition to crucial effects on phosphate and calcium metabolism, FGF23 also has 'off-target' effects notably on the cardiovascular, immune and central nervous systems. Genetic diseases may affect the FGF23 pathway, resulting in either increased FGF23 levels leading to hypophosphatemia (such as in X-linked hypophosphatemia) or defective secretion/action of intact FGF23 inducing hyperphosphatemia (such as in familial tumoral calcinosis). The aim of this review is to provide an overview of FGF23 physiology and pathophysiology in X-linked hypophosphatemia, with a focus on FGF23-associated genetic diseases.


FGF23; PHEX; X-linked hypophosphatemia

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Declaration of Competing Interest The authors declare no conflict of interest.

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