Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, 3000, CA, Rotterdam, The Netherlands.
Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands.
Calcif Tissue Int. 2024 Mar;114(3):255-266. doi: 10.1007/s00223-023-01172-2. Epub 2024 Jan 16.
X-linked hypophosphatemia (XLH) is the most common monogenetic cause of chronic hypophosphatemia, characterized by rickets and osteomalacia. Disease manifestations and treatment of XLH patients in the Netherlands are currently unknown. Characteristics of XLH patients participating in the Dutch observational registry for genetic hypophosphatemia and acquired renal phosphate wasting were analyzed. Eighty XLH patients, including 29 children, were included. Genetic testing, performed in 78.8% of patients, showed a PHEX mutation in 96.8%. Median (range) Z-score for height was - 2.5 (- 5.5; 1.0) in adults and - 1.4 (- 3.7; 1.0) in children. Many patients were overweight or obese: 64.3% of adults and 37.0% of children. All children received XLH-related medication e.g., active vitamin D, phosphate supplementation or burosumab, while 8 adults used no medication. Lower age at start of XLH-related treatment was associated with higher height at inclusion. Hearing loss was reported in 6.9% of children and 31.4% of adults. Knee deformities were observed in 75.0% of all patients and osteoarthritis in 51.0% of adult patients. Nephrocalcinosis was observed in 62.1% of children and 33.3% of adults. Earlier start of XLH-related treatment was associated with higher risk of nephrocalcinosis and detection at younger age. Hyperparathyroidism longer than six months was reported in 37.9% of children and 35.3% of adults. This nationwide study confirms the high prevalence of adiposity, hearing loss, bone deformities, osteoarthritis, nephrocalcinosis and hyperparathyroidism in Dutch XLH patients. Early start of XLH-related treatment appears to be beneficial for longitudinal growth but may increase development of nephrocalcinosis.
X 连锁低磷血症（XLH）是慢性低磷血症最常见的单基因病因，其特征为佝偻病和骨软化症。目前尚不清楚荷兰 XLH 患者的疾病表现和治疗情况。分析了参与荷兰遗传性低磷血症和获得性肾磷酸盐丢失观察性登记处的 XLH 患者的特征。共纳入 80 例 XLH 患者，包括 29 例儿童。对 78.8%的患者进行基因检测，发现 PHEX 突变 96.8%。成人身高中位数（范围）Z 评分-2.5（-5.5；1.0），儿童为-1.4（-3.7；1.0）。许多患者超重或肥胖：64.3%的成人和 37.0%的儿童。所有儿童均接受 XLH 相关药物治疗，如活性维生素 D、磷酸盐补充剂或布罗索尤单抗，而 8 名成人未使用任何药物。XLH 相关治疗开始年龄越小，纳入时身高越高。儿童听力损失发生率为 6.9%，成人听力损失发生率为 31.4%。所有患者中有 75.0%存在膝关节畸形，51.0%的成年患者存在骨关节炎。62.1%的儿童和 33.3%的成人存在肾钙质沉着症。XLH 相关治疗开始越早，肾钙质沉着症的风险越高，且发病年龄越小。儿童甲状旁腺功能亢进超过 6 个月的发生率为 37.9%，成人的发生率为 35.3%。这项全国性研究证实了荷兰 XLH 患者中肥胖、听力损失、骨骼畸形、骨关节炎、肾钙质沉着症和甲状旁腺功能亢进的高患病率。XLH 相关治疗的早期开始似乎有利于纵向生长，但可能会增加肾钙质沉着症的发生。
