Department of Endocrinology and Diabetes, Birmingham Women's and Children's Hospital NHS Trust, Birmingham, UK.
Institute of Applied Health Research, University of Birmingham, Birmingham, UK.
Paediatr Drugs. 2020 Apr;22(2):113-121. doi: 10.1007/s40272-020-00381-8.
X-linked hypophosphataemia (XLH) is due to mutations in phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX) and represents the most common heritable form of rickets. In this condition, the hormone fibroblast growth factor 23 (FGF23) is produced in excessive amounts for still unknown reasons, and causes renal phosphate wasting and suppression of 1,25-dihydroxyvitamin D, leading to low serum phosphate concentrations. Prolonged hypophosphataemia decreases apoptosis of hypertrophic chondrocytes in growth plates (causing rickets) and decreases mineralisation of existing bone (causing osteomalacia). In contrast to historical conventional treatment with oral phosphate supplements and active vitamin D for the last 50 years, the new anti-FGF23 antibody treatment (burosumab) targets the primary pathology by blocking FGF23, thereby restoring phosphate homeostasis. In this review, we describe the changes in treatment monitoring, treatment targets and long-term treatment goals, including future opportunities and challenges in the treatment of XLH in children.
X 连锁低磷血症（XLH）是由于 X 染色体上具有肽内切酶同源性的磷调节基因（PHEX）的突变引起的，是最常见的遗传性佝偻病形式。在这种情况下，由于未知原因，激素成纤维细胞生长因子 23（FGF23）大量产生，并导致肾脏磷酸盐丢失和 1,25-二羟维生素 D 的抑制，从而导致血清磷酸盐浓度降低。长期低磷血症可降低生长板中肥大软骨细胞的凋亡（导致佝偻病），并降低现有骨的矿化（导致骨软化症）。与过去 50 年来口服磷酸盐补充剂和活性维生素 D 的传统常规治疗相比，新的抗 FGF23 抗体治疗（布罗索尤单抗）通过阻断 FGF23 来针对主要病理，从而恢复磷酸盐的体内平衡。在这篇综述中，我们描述了治疗监测、治疗靶点和长期治疗目标的变化，包括 XLH 在儿童治疗方面的未来机遇和挑战。
