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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A translocation causing increased α-Klotho level results in hypophosphatemic rickets and hyperparathyroidism
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A translocation causing increased α-Klotho level results in hypophosphatemic rickets and hyperparathyroidism

机译：易位导致α-Klotho水平升高，导致低磷性rick病和甲状旁腺功能亢进

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摘要

Phosphate homeostasis is central to diverse physiologic processes including energy homeostasis, formation of lipid bilayers, and bone formation. Reduced phosphate levels due to excessive renal loss cause hypophosphatemic rickets, a disease characterized by prominent bone defects; conversely, hyperphosphatemia, a major complication of renal failure, is accompanied by parathyroid hy-perplasia, hyperparathyroidism, and osteodystrophy. Here, we define a syndrome featuring both hypophosphatemic rickets and hyperparathyroidism due to parathyroid hyperplasia as well as other skeletal abnormalities. We show that this disease is due to a de novo translocation with a breakpoint adjacent to α-Klotho. which encodes a β-glucuronidase, and is implicated in aging and regulation of FGF signaling. Plasma α-Klotho levels and β-glucuronidase activity are markedly increased in the affected patient; unexpectedly, the circulating FGF23 level is also markedly elevated. These findings suggest that the elevated a-Klotho level mimics aspects of the normal response to hyperphosphatemia and implicate a-Klotho in the selective regulation of phosphate levels and in the regulation of parathyroid mass and function; they also have implications for the pathogenesis and treatment of renal osteodystrophy in patients with kidney failure.
机译：磷酸盐稳态是多种生理过程的核心，包括能量稳态，脂质双层的形成和骨骼的形成。由于过度的肾脏损失导致磷酸盐水平降低会导致低磷酸盐血症性ets病，这种疾病的特征是明显的骨骼缺陷；相反，高磷血症是肾衰竭的主要并发症，伴有甲状旁腺增生，甲状旁腺功能亢进和骨营养不良。在这里，我们定义了一种由于甲状旁腺增生以及其他骨骼异常而导致的低磷酸盐血症性rick病和甲状旁腺功能亢进的综合征。我们显示该疾病是由于从头易位，断点与α-Klotho相邻。编码β-葡糖醛酸糖苷酶，并与FGF信号的衰老和调节有关。患病患者的血浆α-Klotho水平和β-葡萄糖醛酸苷酶活性显着增加；出乎意料的是，循环中的FGF23水平也明显升高。这些发现表明，升高的α-Klotho水平模仿了对高磷血症的正常反应，并暗示α-Klotho参与了磷水平的选择性调节以及甲状旁腺质量和功能的调节。它们也对肾衰竭患者肾性骨营养不良的发病机理和治疗具有重要意义。

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