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.
Paris Descartes University, EA2496, Faculty of Dental Surgery, Montrouge, France.
Metabolism. 2020 Feb;103S:153865. doi: 10.1016/j.metabol.2019.01.006. Epub 2019 Jan 19.
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.
磷酸盐是包括骨骼发育、骨矿化、膜组成、核苷酸结构、维持血浆 pH 值和细胞信号在内的几种生理途径的基石。肾脏在磷酸盐稳态中起着关键作用，三种激素在肾脏磷酸盐处理或肠道吸收中具有重要功能：甲状旁腺激素 (PTH)、成纤维细胞生长因子 23 (FGF23) 和 1-25-二羟维生素 D (1,25(OH)2D)。FGF23 主要由骨细胞合成；它是一种直接的排磷酸盐因子，还抑制 1,25(OH)2D 和 PTH。除了对磷酸盐和钙代谢有重要影响外，FGF23 还对心血管、免疫和中枢神经系统有“非靶向”作用。遗传疾病可能会影响 FGF23 途径，导致 FGF23 水平升高导致低磷酸盐血症（如 X 连锁低磷酸盐血症），或完整 FGF23 的分泌/作用缺陷导致高磷酸盐血症（如家族性肿瘤性钙质沉着症）。本综述的目的是概述 X 连锁低磷酸盐血症中 FGF23 的生理学和病理生理学，重点介绍与 FGF23 相关的遗传疾病。
