Drezner M K
Departments of Medicine and Cellular Biology, Duke University Medical Center, Durham, North Carolina 27719, USA.
Kidney Int. 2000 Jan;57(1):9-18. doi: 10.1046/j.1523-1755.2000.00807.x.
PHEX gene and hypophosphatemia. X-linked hypophosphatemia (XLH) and tumor-induced osteomalacia (TIO) are diseases that have in common abnormal proximal renal tubular function resulting in increased renal clearance of inorganic phosphorus and hypophosphatemia. The recent discovery of the PHEX gene has provided new insights to these disorders. In this regard, identification of the PHEX gene product as a membrane-bound endopeptidase suggests that the pathophysiologic cascade underlying XLH likely involves inactivation mutations of the gene causing a failure to clear an active hormone, phosphatonin, from the circulation. The presence of this hormone through unknown mechanisms decreases the sodium-dependent phosphate cotransporter in the kidney, resulting in impaired phosphate transport. In contrast, TIO likely evolves secondary to tumor overproduction of the putative phosphatonin, which exerts physiologic function despite efforts to counteract the resultant hypophosphatemia with overproduction of PHEX transcripts that are insufficient to accommodate the enhanced substrate load. These potential pathophysiologic mechanisms for XLH and TIO provide valuable inroads to understanding phosphate homeostasis, as well as vitamin D metabolism, bone mineralization, and calcium metabolism.
PHEX基因与低磷血症。X连锁低磷血症（XLH）和肿瘤诱导的骨软化症（TIO）是一类具有共同特征的疾病，即近端肾小管功能异常，导致无机磷的肾脏清除率增加和低磷血症。PHEX基因的最新发现为这些疾病提供了新的见解。在这方面，PHEX基因产物被鉴定为一种膜结合内肽酶，这表明XLH潜在的病理生理级联反应可能涉及该基因的失活突变，导致无法从循环中清除一种活性激素——磷调节素。这种激素通过未知机制降低了肾脏中钠依赖性磷酸盐共转运体的水平，导致磷酸盐转运受损。相比之下，TIO可能继发于肿瘤过度产生假定的磷调节素，尽管机体努力通过过度产生不足以适应增加的底物负荷的PHEX转录本来抵消由此导致的低磷血症，但该激素仍发挥生理功能。XLH和TIO的这些潜在病理生理机制为理解磷酸盐稳态以及维生素D代谢、骨矿化和钙代谢提供了宝贵的切入点。
