Inherited hypophosphatemic disorders in children and the evolving mechanisms of phosphate regulation
Inherited hypophosphatemic disorders in children and the evolving mechanisms of phosphate regulation
复制标题
DOI：
10.1007/s11154-008-9075-3
复制
发表时间：
2008-06-01
影响因子：
8.2
通讯作者：
Jueppner, Harald
中科院分区：
文献类型：
--
作者：
Bastepe, Murat;Jueppner, Harald
磷是多种细胞功能所必需的，是骨骼中的一种重要矿物质。儿童的低磷血症会导致软骨病，导致生长异常，通常还会导致骨骼畸形。引起低血磷的各种原因包括与尿磷排泄增加相关的遗传性疾病，包括常染色体显性遗传性低磷血症(ADHR)、X连锁低磷血症(XLH)、常染色体隐性遗传性低磷血症(ARHP)和遗传性低磷血症伴高钙尿症(HHRH)。最近的遗传分析和随后的生化和动物研究揭示了几个新的分子，它们似乎在调节肾脏磷酸盐的处理方面发挥了关键作用。其中包括一种在骨骼中大量表达的蛋白质，成纤维细胞生长因子23(FGF23)，它已被证明是一种循环激素，可以抑制肾脏对磷酸盐的管状重吸收。另外两种骨特异性蛋白，PHEX和牙本质基质蛋白1(DMP1)似乎对于限制成纤维细胞生长因子23的表达是必要的，从而允许足够的肾脏保护磷酸盐。本文综述了遗传性低磷血症的临床、生化和遗传学特征，并介绍了目前对控制磷稳态的激素和分子机制的了解。
Phosphorous is essential for multiple cellular functions and constitutes an important mineral in bone. Hypophosphatemia in children leads to rickets resulting in abnormal growth and often skeletal deformities. Among various causes of low serum phosphorous are inherited disorders associated with increased urinary excretion of phosphate, including autosomal dominant hypophosphatemic rickets (ADHR), X-linked hypophosphatemia (XLH), autosomal recessive hypophosphatemia (ARHP), and hereditary hypophosphatemic rickets with hypercalciuria (HHRH). Recent genetic analyses and subsequent biochemical and animal studies have revealed several novel molecules that appear to play key roles in the regulation of renal phosphate handling. These include a protein with abundant expression in bone, fibroblast growth factor 23 (FGF23), which has proven to be a circulating hormone that inhibits tubular reabsorption of phosphate in the kidney. Two other bone-specific proteins, PHEX and dentin matrix protein 1 (DMP1), appear to be necessary for limiting the expression of fibroblast growth factor 23, thereby allowing sufficient renal conservation of phosphate. This review focuses on the clinical, biochemical, and genetic features of inherited hypophosphatemic disorders, and presents the current understanding of hormonal and molecular mechanisms that govern phosphorous homeostasis.