法布莱氏病的发病机制、诊断及治疗方法的研究进展

Pathogenesis,diagnosis and therapeutic methods of Fabry disease:research advances

法布莱氏病是一种X连锁隐性遗传病,由定位于Xq22的α-半乳糖苷酶A(alpha-galactosidaseA,α-GalA)基因突变使酶失活造成。α-GalA的缺乏导致N-脂酰鞘氨醇己三糖苷在全身细胞、组织和器官中累积而引起血液循环障碍并进一步导致心、肾功能衰竭和神经系统紊乱而死亡。一般检测血浆、尿和外周血白细胞中α-GalA的活性和蛋白含量作为诊断法布莱氏病的指标。治疗方法有止痛、酶替代疗法、肾移植、分子伴侣和竞争性抑制剂及基因疗法。利用转基因技术及其他一些前沿技术,将有可能彻底消除这种长期困扰人类的溶酶体贮积病。

Fabry disease is an inherited deficiency of the lysosomal hydrolase alpha-galactosidase A due to mutations in the Gal gene at Xq22. The resulting inability to catabolize glycosphingolipids causes progressive accumulation of globotriaosylceramide（Gb3） in body ceils,tissues and organs, resulting in death due to cardiovascular, cerebrovascular, renal dysfunction and neural disorders. Generally, Fabry disease is diagnosed through determining the concentration of α-galactosidase activity and protein in plasma, peripheral leukocytes and urine. There are several methods for therapy such as acesodyne, enzyme replacement, kidney transplantation, chemical chaperones,competitive inhibitors, and gene therapy. Lysosomal storage diseases will be thoroughly cleared up by resorting to transgenic technology or other advanced technologies.