Serum transferrin carrying the xeno-tetrasaccharide NeuAc-Gal-GlcNAc2 is a biomarker of ALG1-CDG.
Serum transferrin carrying the xeno-tetrasaccharide NeuAc-Gal-GlcNAc2 is a biomarker of ALG1-CDG.
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DOI：
10.1007/s10545-015-9884-y
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发表时间：
2016-01
影响因子：
4.2
通讯作者：
Eklund EA
中科院分区：
文献类型：
--
作者：
Bengtson P;Ng BG;Jaeken J;Matthijs G;Freeze HH;Eklund EA
ALG1-CDG（以前称为 CDG-Ik）是先天性糖基化障碍 (CDG) 的一种亚型，其中遗传缺陷破坏了 N-糖基化所需的脂质连接寡糖前体的合成。研究这些疾病的第一步涉及血清转铁蛋白 (TF) 低糖基化的证明。迄今为止，尚无该 CDG 亚型的特异性生物标志物。采用 LC/MS 方法分析 ALG1-CDG、PMM2-CDG、疑似 CDG 患者和酗酒者的血清。我们展示了质谱数据与酶消化数据相结合，表明血清 TF 上出现的由两种 N-乙酰氨基葡萄糖、一种半乳糖和一种唾液酸组成的四糖的存在，是这种特定 CDG 亚型的生物标志物。这是首次对血清 TF 的分析可以提示特定的 CDG I 型亚型，我们建议在临床中使用这种四糖来指导 ALG1-CDG 诊断过程。
ALG1-CDG (formerly CDG-Ik) is a subtype of congenital disorders of glycosylation (CDG) where the genetic defect disrupts the synthesis of the lipid-linked oligosaccharide precursor required for N-glycosylation. The initial step in the investigation for these disorders involves the demonstration of hypoglycosylated serum transferrin (TF). There are no specific biomarkers of this CDG subtype known to date. An LC/MS approach was used to analyze sera from patients with ALG1-CDG, PMM2-CDG, suspected CDG and individuals with alcohol abuse. We show mass spectrometric data combined with data from enzymatic digestions that suggest the presence of a tetrasaccharide consisting of two N-acetylglucosamines, one galactose and one sialic acid, appearing on serum TF, is a biomarker of this particular CDG subtype. This is the first time analysis of serum TF can suggest a specific CDG Type I subtype and we suggest this tetrasaccharide be used in the clinic to guide the ALG1-CDG diagnostic process.