Autosomal dominant hypophosphatemia (ADH) causes rickets, osteomalacia, and taurodontism due to heterozygous mutations in FGF23, which inhibit the inactivation (cleavage) of the encoded protein, the hormone fibroblast growth factor 23 (FGF23). Iron deficiency increases FGF23 mRNA expression and recent evidence suggests that the recurrent, late‐onset, or waxing‐waning hypophosphatemic phenotype may be linked to synchronous variations in iron status. The fact that most adult symptomatic ADH patients are females during reproductive age supports the notion of a gene‐environmental interaction. Practically all symptomatic hypophosphatemic patients described in the recent literature were also iron deficient (with/without anemia) at presentation, when measured. Given its interaction with FGF23, correcting iron deficiency should therefore also correct FGF23 excess. Following the original report of successful phenotype reversal in an iron‐deficient ADH child using oral iron supplementation in 2015, more evidence has emerged that supports the use of the element iron to restore homoeostasis of the element phosphorus (in addition to its own). We put into perspective the recent evidence and add 14 years observational data on the original case that demonstrates the correlation of serum phosphorus and renal tubular phosphate reabsorption in mass per unit volume of glomerular filtrate (TmP/GFR) with serum ferritin. Presentation and relapse of ADH, 12 years apart, occurred during iron deficiency, and the onset of menstrual periods was associated with relapse. Here we propose management guidance for patients affected by ADH throughout the lifespan based on iron stores. Because ferritin correlates best with hypophosphatemia historically, and in long‐term observation of the originally treated case, it should be used as the monitoring tool and kept in the normal range. Women with ADH who are of reproductive age and other risk groups require supplementation with oral iron using WHO guidelines. Treatment of this form of FGF23 excess may not require phosphate and active vitamin D, or burosumab. © 2020 American Society for Bone and Mineral Research

中文翻译：

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预防和治疗常染色体显性低磷血症的Ri病和骨软化症的口服铁剂。

常染色体显性遗传性低磷血症（ADH）会由于FGF23中的杂合突变而导致病，骨软化症和牛头牙症，从而抑制了编码蛋白荷尔蒙成纤维细胞生长因子23（FGF23）的失活（裂解）。铁缺乏会增加FGF23 mRNA的表达，最近的证据表明，低磷酸盐表型的复发，迟发或逐渐减弱可能与铁状态的同步变化有关。大多数成年人有症状的ADH患者在生育年龄是女性这一事实支持了基因-环境相互作用的概念。实际上，最新文献中描述的所有有症状的低磷酸盐血症患者在测量时也都表现为铁缺乏症（有/无贫血）。鉴于其与FGF23的相互作用，因此，纠正铁缺乏症也应纠正FGF23过量。继2015年使用铁补充剂在铁缺乏的ADH儿童中成功逆转表型的原始报道之后，出现了更多的证据支持使用元素铁恢复元素磷的同态性（除了自身）。我们对最新证据进行了展望，并在原始案例中添加了14年的观察数据，该案例证明了血清磷和肾小管磷酸盐重吸收与单位体积肾小球滤过液（TmP / GFR）的质量与血清铁蛋白的相关性。缺铁期间ADH的出现和复发（相隔12年）发生，并且月经的发作与复发有关。在此，我们根据铁的存储量为整个生命周期中受ADH影响的患者提供管理指导。由于铁蛋白在历史上与低磷血症最相关，在长期观察最初治疗的病例时，应将其用作监测工具并保持在正常范围内。处于生殖年龄和其他危险人群的患有ADH的女性需要根据WHO指南补充口服铁剂。这种形式的FGF23过量的治疗可能不需要磷酸盐和活性维生素D或burosumab。©2020美国骨与矿物质研究学会 处于生殖年龄和其他危险人群的患有ADH的女性需要根据WHO指南补充口服铁剂。这种形式的FGF23过量的治疗可能不需要磷酸盐和活性维生素D或burosumab。©2020美国骨与矿物质研究学会 处于生殖年龄和其他危险人群的患有ADH的女性需要根据WHO指南补充口服铁剂。这种形式的FGF23过量的治疗可能不需要磷酸盐和活性维生素D或burosumab。©2020美国骨与矿物质研究学会