Etiology and Pathogenesis of CDG Syndrome

CDG综合征是新近发现的一种遗传性疾病，具有独特的神经系统和全身表现，其病因和发病机制目前尚不清楚。我们试图分析这种疾病患者的体细胞中的分子异常。在几种溶酶体酶中，β-氨基己糖苷酶和α-岩藻糖苷酶在血清中表现出较高的催化活性。后者的电聚焦模式显示蛋白质带增加，更多地向阳极移动，表明含有唾液酸的糖蛋白分子增加。免疫印迹法检测到血清转铁蛋白和抗凝血酶含有小分子异常分子。在培养的成纤维细胞中，β-氨基己糖苷酶的成熟α亚基增加，但细胞外正常。在这些细胞中，有两名患者的磷酸甘露聚糖酶活性极低。这种异常可能导致细胞内甘露糖1-磷酸和GDP-甘露糖的减少，导致糖蛋白分子糖基化不足。

CDG syndrome is a recently identified hereditary disease with unique neurological and general somatic manifestations, and its etiology and pathogenesis are have been unknown up till recently. We tried to analyze molecular abnormalities in somatic cells from patients with this disease. Among several lysosomal enzymes, beta-hexosaminidase and alpha-fucosidase showed high catalytic activities in serum. The electrofocusing pattern of the latter revealed an increase of protein bands moving more toward the anode, indicating an increase of sialic acid-containing glyco-protein molecules. Serum transferrin and antithrombin contained abnormal molecules of small size detected by immunoblotting. The mature alpha-subunit of beta-hexosaminidase was increased in cultured fibroblasts, but normal extracellularly. In these cells, phosphomannomutase activity was extremely low in two patients. This abnormality probably induces a decrease of intra-cellular mannose 1-phosphate and GDP-mannose, resulting in insufficient glycosylation of glycoprotein molecules.