Failure of short-term mannose therapy of patients with carbohydrate-deficient glycoprotein syndrome type 1A
Failure of short-term mannose therapy of patients with carbohydrate-deficient glycoprotein syndrome type 1A
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DOI：
10.1080/080352598750013680
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发表时间：
1998-08-01
期刊：
影响因子：
3.8
通讯作者：
Skovby, F
中科院分区：
文献类型：
--
作者：
Kjaergaard, S;Kristiansson, B;Skovby, F
碳水化合物缺乏糖蛋白综合征1A型（CDGS 1A）是一种遗传性疾病，由于无法产生足够的脂质连接的寡糖前体或将糖链转移到许多糖蛋白而导致多系统异常。来自这些患者的培养的成纤维细胞具有降低的甘露糖掺入糖蛋白中，这可以通过向培养基中添加D-甘露糖来校正。因此，提供膳食甘露糖以提高体内甘露糖浓度可能会纠正患者中的一些糖基化不足。5例15个月~ 14岁的CDGS 1A患儿接受D-甘露糖100 mg/kg肠内补充，每3 h 1次，共9 d。平均S-甘露糖水平从32 μ M（范围22-42 μ M）增加到72 μ M（范围39-103 μ M）的谷值。未观察到严重副作用。令人惊讶的是，四种糖蛋白（转铁蛋白，α 1-抗胰蛋白酶，抗凝血酶和甲状腺素结合球蛋白）的平均血清浓度趋于降低，碳水化合物缺乏转铁蛋白（CDT）的平均血清浓度增加。此外，这些糖蛋白和蛋白C的最初存在的异常亚型变得更加突出和/或出现额外的异常亚型。这项短期试验不支持甘露糖对CDGS 1A患者糖基化缺陷的益处。
Carbohydrate-deficient glycoprotein syndrome type 1A (CDGS1A) is an inherited disorder with multi-systemic abnormalities resulting from failure to generate sufficient lipid-linked oligosaccharide precursor or to transfer the sugar chain to many glycoproteins. Cultured fibroblasts from these patients have reduced incorporation of mannose into glycoproteins which can be corrected by adding D-mannose to the culture medium. Providing dietary mannose to elevate mannose concentrations in vivo therefore might remedy some of the underglycosylation in the patients. Five children with CDGS1A aged 15 months to 14 y completed a protocol of enteral supplementation with D-mannose 100 mg/kg every 3 h for 9 d. The mean S-mannose level increased from 32 mu M (range 22-42 mu M) to a trough value of 72 mu M (range 39-103 mu M). NO serious side effects were observed. Surprisingly, the mean serum concentration of four glycoproteins (transferrin, alpha 1-antitrypsin, antithrombin, and thyroxine-binding globulin) tended to decrease, and the mean serum concentration of carbohydrate-deficient transferrin (CDT) increased. Furthermore, the initially present abnormal isoforms of these glycoproteins and of protein C became more prominent and/or additional abnormal isoforms appeared. This short-term trial does not support a benefit of mannose to the deficient glycosylation of CDGS1A patients.