Screening for congenital disorders of glycosylation in the first weeks of life
Screening for congenital disorders of glycosylation in the first weeks of life
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DOI：
10.1007/s10545-012-9531-9
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发表时间：
2013-09-01
影响因子：
4.2
通讯作者：
Koerner, Christian
中科院分区：
文献类型：
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作者：
Thiel, Christian;Messner-Schmitt, Dorothea;Koerner, Christian
由于糖结合物N-和O-糖基化的复杂代谢途径的缺陷，遗传性单基因人类疾病被称为‘先天性糖基化障碍’(CDG)。由于近年来这些缺陷的数量迅速增加，其中大多数是严重的多系统表型，儿科医生的兴趣也增加了，导致怀疑CDG的患者样本数量增加。一般来说，CDG的主要诊断始于对血清转铁蛋白糖基化状态的调查，转铁蛋白是该领域多年来的‘金标准’。然而，转铁蛋白的使用表明，从出生到生命第3个月的时间跨度是一个分析问题。在这个发育阶段，与蛋白质连接的N-寡糖部分通常是不完整的，类似于CDG模式，并导致假阳性结果。因此，有必要为这一寿命建立可靠和快速的诊断程序。在这里，我们显示血清α-1-抗胰蛋白酶的糖基化状态在出生后不久就已经完全存在，这使得在生命的头几周研究CDG的另一种诊断方法成为可能。该方法可以很容易地在每个实验室建立，特别是有转铁蛋白分析经验的实验室。
Inherited monogenetic human disorders due to deficiencies in the complex metabolic pathways for N- and O-glycosylation of glycoconjugates are termed 'congenital disorders of glycosylation' (CDG). Since the number of these defects with mostly severe multisystemic phenotypes has been rapidly expanding in recent years, the interest of paediatricians has also increased resulting in a rising amount of patient samples with the suspicion of CDG. In general, primary diagnostics for CDG start with investigations on the glycosylation state of serum transferrin, the 'gold standard' in the field for many years. However, the use of transferrin shows an analytical problem in the time span from birth up to the 3rd month of life. In this developmental period oligosaccharide moieties N-linked to proteins are often incomplete, resembling a CDG pattern and leading to false-positive results. It is therefore necessary to establish a reliable and fast diagnostic procedure for this span of life. Here we show that the glycosylation state of serum alpha-1-antitrypsin is already fully existent shortly after birth allowing an alternative diagnostic approach for the investigation of CDG in the first weeks of life. The method can easily be established in every laboratory especially with previous experience in transferrin analysis.