Research on the basic defect of carbohydrate-deficient glycoprotein syndrome

碳水化合物缺乏糖蛋白（CDG）综合征是一种新认识的遗传性疾病，其特征是血清中亚洲铁蛋白和二亚铁蛋白的出现。我们之前报道过患者转铁蛋白上的糖链在结构上是正常的，天冬酰胺n链上的糖链在一个或两个可能的糖基化位点上存在缺陷。在这项研究中，我们分析了从前体到脂联寡糖的代谢途径。当CDG成纤维细胞负载[3H]氨基葡萄糖并分析脂链低聚糖中间体时，CDG成纤维细胞中的中间体减少而无特异性阻断。然后我们加载了[3H]甘露糖，并分析了脂链低聚糖中间体。我们在这一途径中未发现任何代谢阻滞。最后，我们加载了[3H]甲羟戊酸，并发现了从脱氢多酚到多酚的代谢阻滞。我们已经得出结论，糖蛋白缺乏糖链的出现可能是由于脱氢苯酚还原功能的部分缺乏引起的^<2)>。据报道，利用脐带血中缺乏糖的糖蛋白进行CDG综合征的产前诊断是不可能的，因为碳水化合物缺乏糖蛋白出现在出生后。为了检测细胞内糖蛋白的异常加工，我们研究了培养的CDG成纤维细胞中的溶酶体酶蛋白。虽然我们没有发现任何异常糖基化的酶蛋白，但我们发现β -己糖氨酸酶蛋白α链增加，提示己糖氨酸酶蛋白加工异常^<3)>。

The carbohydrtae-deficient glycoprotein (CDG) syndrome is newly recongized genetic disorder characterize by apppearance of serum asialo-and disialo-transferrin. We have previously reported that the sugar chain attached to transferrin in the patients is structurally normal and a defect in asparagine N-linked sugar chain in one or two of the possible glycosylation sites.In this study we have analyzed metabolic pathways from precursors to lipid linked oligosaccharide. When CDG fibroblasts were loaded with [3H] glucosamine and analyzed lipid linked oligosaccharide intermediates, the intermediates in CDG fibroblasts were decreased without specific block. Then we have loaded [3H] mannose and analyzed lipid linked oligosaccharide intermediates. We could not find any metabokic block in this pathway. Finally we have loaded [3H] mevalonic acid and found a metabolic block in a step from dehydrodolicol to dolicol. We have concluded that appearance of glycoproteins lacking sugar chain may caused by a partial deficiency of dehydrodolicol reduction^<2)>.Prenatal diagnosis of CDG syndrome using carbohydrate-deficient glycoprotein in cordblood has been reported to be impossible, because carbohydrate-deficient glycooproteins appear after birth. To detect abnormal processing of intracellular glycoprotein, we have studied lysosomal enzyme proteins in cultures CDG fibroblasts. Although we could not find any abnormally glycosylated enzyme proteins, we have found an increase in alpha chain of beta hexosaminidase protein, suggesting abnormal processing of hexosaminidase protein^<3)>.