Dahir Kathryn, Roberts Mary Scott, Krolczyk Stan, Simmons Jill H
Endocrinology and Diabetes, Vanderbilt University Medical Center, Nashville, Tennessee.
Ultragenyx Pharmaceutical Inc, Novato, California.
J Endocr Soc. 2020 Oct 14;4(12):bvaa151. doi: 10.1210/jendso/bvaa151. eCollection 2020 Dec 1.
X-linked hypophosphatemia (XLH) is a rare, hereditary, progressive musculoskeletal disease that often causes pain and short stature, as well as decreased physical function, mobility, and quality of life. Hypophosphatemia in XLH is caused by loss of function mutations in the phosphate-regulating endopeptidase homolog X-linked () gene, resulting in excess levels of the phosphate-regulating hormone fibroblast growth factor 23 (FGF23), which leads to renal phosphate wasting and decreased serum 1,25-dihydroxyvitamin D production. Historically, treatment options were limited to oral phosphate and active vitamin D analogues (conventional management) dosed several times daily in an attempt to improve skeletal mineralization by increasing serum phosphorus. The recent approval of burosumab, a fully human monoclonal antibody to FGF23, has provided a new, targeted treatment option for patients with XLH. This review summarizes our current understanding of XLH, the safety and efficacy of conventional management and burosumab, existing recommendations for managing patients, and unanswered questions in the field.
X连锁低磷血症（XLH）是一种罕见的遗传性进行性肌肉骨骼疾病，常导致疼痛和身材矮小，以及身体功能、活动能力和生活质量下降。XLH中的低磷血症是由磷酸盐调节内肽酶同源物X连锁（PHEX）基因突变导致功能丧失引起的，导致磷酸盐调节激素成纤维细胞生长因子23（FGF23）水平过高，进而导致肾脏磷酸盐流失和血清1,25-二羟维生素D生成减少。从历史上看，治疗选择仅限于口服磷酸盐和活性维生素D类似物（传统治疗），每天给药数次，试图通过提高血清磷来改善骨骼矿化。最近，布罗索尤单抗（一种针对FGF23的全人单克隆抗体）获批，为XLH患者提供了一种新的靶向治疗选择。本综述总结了我们目前对XLH的认识、传统治疗和布罗索尤单抗的安全性和有效性、现有患者管理建议以及该领域尚未解决的问题。
