Department of Medicine, Division of Endocrinology & Center for Bone Quality, Leiden University Medical Center, Leiden, the Netherlands.
RVRH-XLH, French XLH patient organization, 20 rue Merlin de Thionville, 92150 SURESNES, France.
Arch Pediatr. 2021 Oct;28(7):612-618. doi: 10.1016/j.arcped.2021.09.005. Epub 2021 Sep 28.
X-linked hypophosphatemia (XLH) is a rare inheritable disorder of phosphate handling due to loss of function mutations of the PHEX gene, associated with increased production of FGF23 and impaired bone mineralization. In children, the disease's most common manifestations are bowing deformities of the lower limbs, short stature, and spontaneous dental abscesses. In adults, these are osteomalacia, insufficiency fractures, and enthesopathies associated with bone and joint pain. The XLH patient's journey with the disease may be difficult, reflecting concerns and experiences globally common to all patients with rare genetic diseases. Delays in diagnosis often preclude an optimal treatment outcome. Under-treatment is common as treating physicians, particularly those not familiar with the disease, tend to err on the side of caution, often choosing safety over efficacy. Physical abnormalities, pain, diminished function, and impaired mobility tend not only to isolate the XLH patient from his peers but also to have a significant psychological effect, eventually leading to significant impairment in quality of life. Significant advances in understanding the pathophysiology of XLH, the availability of a very comprehensive Evidence-based Guideline for the diagnosis and management of XLH, and the successful development of an effective and safe disease-specific novel therapy for XLH, have paved the way for a significant improvement in the management of this rare disorder of phosphate metabolism, heralding a significant improvement in the disease's outcome measures. Additional data from long-term observational studies and randomized controlled trials are eagerly awaited to consolidate these promising developments in the field of this rare disease.
X 连锁低磷血症（XLH）是一种罕见的遗传性磷酸盐代谢紊乱疾病，由于 PHEX 基因突变导致功能丧失，与 FGF23 产生增加和骨矿化受损有关。在儿童中，该疾病最常见的表现是下肢弯曲畸形、身材矮小和自发性牙脓肿。在成人中，这些是骨软化症、骨不连和与骨骼和关节疼痛相关的肌腱病。XLH 患者的疾病之旅可能很艰难，反映了全球所有罕见遗传疾病患者普遍存在的担忧和经历。诊断延迟常常导致无法获得最佳治疗效果。治疗不足很常见，因为治疗医生，特别是那些不熟悉该疾病的医生，往往过于谨慎，常常选择安全性而不是疗效。身体异常、疼痛、功能减退和活动能力受损不仅使 XLH 患者与同龄人隔离，而且对其心理产生重大影响，最终导致生活质量显著受损。对 XLH 病理生理学的理解取得了重大进展，制定了全面的基于证据的 XLH 诊断和管理指南，并且成功开发了针对 XLH 的有效且安全的新型疾病特异性治疗方法，为这种罕见的磷酸盐代谢紊乱疾病的管理铺平了道路，预示着疾病预后的显著改善。迫切需要来自长期观察性研究和随机对照试验的更多数据，以巩固这一罕见疾病领域的这些有希望的进展。
