Background

Glycosylation is one of the most complex post-translational modifications of proteins and lipids, notably requiring many glycosyltransferases, glycosidases and sugar transporters encoded by about 1–2% of all human genes. Deleterious variants in any of them may result in improper protein or lipid glycosylation, thus yielding the so-called ‘congenital disorders of glycosylation’ or CDG.

Scope of review

We first review the current state of knowledge on the common blood and cellular glycoproteins used in the biochemical screening of CDG, as well as the emerging ones for an improved diagnosis. We then provide an overview of the current state-of-the-art methodologies ranging from gel electrophoresis to mass spectrometry to measure improper glycosylation. Finally, we discuss how additional tools such as metabolomics and microfluidics can be added to the current toolbox to better diagnose and delineate CDG.

Major Conclusions

Combining several biochemical indicators and related methods is often required to cope with the large clinical heterogeneity of CDG and establish a definitive diagnosis.

General significance

This review aims to critically present current available CDG biochemical biomarkers and dedicated methods in the context of highly diverse glycosylation pathways and related inherited diseases.

中文翻译：

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CDG生化检查：我们站在哪里？

背景

糖基化是蛋白质和脂质最复杂的翻译后修饰之一，特别是需要约1-2％的人类基因编码的许多糖基转移酶，糖苷酶和糖转运蛋白。它们中的任何一种有害变体都可能导致蛋白质或脂质糖基化不当，从而产生所谓的“先天性糖基化疾病”或CDG。

审查范围

我们首先回顾一下CDG生化筛查中所用的常见血液和细胞糖蛋白的知识现状，以及用于改善诊断的新兴知识。然后，我们提供了从凝胶电泳到质谱法测量不正确糖基化的最新技术方法的概述。最后，我们讨论如何将其他工具（如代谢组学和微流体学）添加到当前工具箱中，以更好地诊断和描绘CDG。

主要结论

通常需要结合几种生化指标和相关方法来应对CDG的巨大临床异质性并建立明确的诊断。

一般意义

这篇综述的目的是在高度多样的糖基化途径和相关遗传疾病的背景下，严格地介绍当前可用的CDG生化生物标记物和专用方法。