X-linked hypophosphatemia (XLH), the most prevalent heritable renal phosphate (Pi) wasting disorder, is caused by deactivating mutations of PHEX. Consequently, circulating phosphatonin FGF23 becomes elevated and hypophosphatemia in affected children leads to rickets with skeletal deformity and reduced linear growth while affected adults suffer from osteomalacia and forms of ectopic mineralization. In 2015, we reported uniquely mild XLH in six children and four of their mothers carrying the non-coding PHEX 3'-UTR mutation c.*231A>G. Herein, we characterize this mild XLH variant by comparing its features in 30 individuals to 30 age- and sex-matched patients with XLH but without the 3'-UTR mutation. The "UTR" and "XLH" groups, both comprising 17 children (2 to 17 years, 3 girls) and 13 adults (23 to 63 years, 10 women), had mean ages of 23 years. Only 43% of the UTR group versus 90% of the XLH group had received medical treatment for their disorder, including 0% versus 85% of the females, respectively (ps < .0001). The UTR group was taller: mean ± SD height Z-score (HZ) -1.0 ± 1.0 versus -2.0 ± 1.4 (p = .0034), with significantly greater height for females (-0.9 ± 0.7 versus -2.3 ± 1.4; p = .0050) but not males (-1.2 ± 1.1 versus -1.9 ± 1.5; p = .1541), respectively. Mean ± SD "arm span Z-score" (AZ) did not differ between the UTR -0.8 ± 1.3 versus XLH -1.3 ± 1.8 groups (p = .2269). Consequently, the UTR group was more proportionate with a mean ∆Z (AZ - HZ) of 0.1 ± 0.6 versus 0.7 ± 1.0 (p = .0158), respectively. Compared to the XLH group, the UTR group had significantly higher fasting serum Pi and renal tubular threshold maximum for phosphorus per glomerular filtration rate (TmP/GFR) (ps ≤ .0060), serum FGF23 concentrations within the reference range (p = .0068), and similar serum alkaline phosphatase levels (p = .6513). UTR lumbar spine bone mineral density Z-score was higher (p = .0343). Thus, the 3'-UTR variant of XLH is distinctly mild, especially in girls and women, posing challenges for its recognition and management. © 2020 American Society for Bone and Mineral Research.

中文翻译：

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X 连锁低磷血症：与 PHEX 3'-UTR 突变 c.*231A>G 相关的独特轻度疾病（回顾性病例对照研究）。

X 连锁低磷血症 (XLH) 是最普遍的遗传性肾磷酸盐 (Pi) 消耗性疾病，是由 PHEX 的失活突变引起的。因此，受累儿童的循环磷酸化因子 FGF23 升高和低磷血症导致佝偻病伴骨骼畸形和线性生长减慢，而受累成人则患有骨软化症和异位矿化形式。2015 年，我们报道了 6 名儿童和 4 名母亲携带非编码 PHEX 3'-UTR 突变 c.*231A>G 的独特轻度 XLH。在这里，我们通过比较 30 名个体与 30 名年龄和性别匹配但没有 3'-UTR 突变的 XLH 患者的特征来表征这种轻度 XLH 变异。“UTR”和“XLH”组，均包括 17 名儿童（2 至 17 岁，3 名女孩）和 13 名成人（23 至 63 岁，10 名女性），平均年龄为 23 岁。只有 43% 的 UTR 组和 90% 的 XLH 组接受了药物治疗，分别包括 0% 和 85% 的女性 (ps < .0001)。UTR 组更高：平均 ± SD 身高 Z 分数 (HZ) -1.0 ± 1.0 对 -2.0 ± 1.4 (p = .0034)，女性的身高明显更高（-0.9 ± 0.7 对 -2.3 ± 1.4；p = .0050）但不是男性（-1.2 ± 1.1 对 -1.9 ± 1.5；p = .1541）。UTR -0.8 ± 1.3 与 XLH -1.3 ± 1.8 组之间的平均值 ± SD“臂展 Z 分数”(AZ) 没有差异 (p = .2269)。因此，UTR 组的平均 ΔZ (AZ - HZ) 分别为 0.1 ± 0.6 和 0.7 ± 1.0 (p = .0158)，更加成比例。与 XLH 组相比，UTR 组的空腹血清 Pi 和肾小管最大磷/肾小球滤过率阈值 (TmP/GFR) (ps ≤ .0060)、参考范围内的血清 FGF23 浓度 (p = .0068) 和相似的血清碱性磷酸酶水平 (p = .6513)。UTR 腰椎骨矿物质密度 Z 评分较高 (p = .0343)。因此，XLH 的 3'-UTR 变体明显温和，尤其是在女孩和女性中，对其识别和管理提出了挑战。© 2020 美国骨与矿物研究学会。特别是在女孩和妇女中，对其认可和管理构成挑战。© 2020 美国骨与矿物研究学会。特别是在女孩和妇女中，对其认可和管理构成挑战。© 2020 美国骨与矿物研究学会。