Diseases of glycosylation

Diseases of glycosylation, usually referred to as congenital disorders of glycosylation (CDG), are rare inherited disorders ascribing defects of nucleotide-sugar biosynthesis and transport, glycosyl transfer events and vesicular transport. Most CDGs cause neurological impairment ranging from severe psychomotor retardation to mild intellectual disability. Defects in N-glycosylation are the main cause of CDGs (Marquardt & Denecke 2003, Grunewald et al. 2002, Hennet 2012, Goreta et al. 2012) and can be identified by a characteristic abnormal isoelectric focusing profile of plasma transferrin (Jaeken et al. 1984, Stibler & Jaeken 1990). Disorders of O-glycosylation, glycosaminoglycan and glycolipid metabolism have recently been discovered and, together with N-glycosylation, represent the major pathways affected by glycan biosynthetic disorders (Freeze 2006, Jaeken 2011). In addition, glycosylation diseases associated with the enzymes that mediate the biosynthesis of glycosylation precursors are described in this section. As the number of these disorders has increased, nomenclature has been simplified so that now, the name of the mutant gene is followed by the abbreviation CDG (Jaeken et al. 2009). Effective therapies for most types of CDGs are so far not available (Thiel & Korner 2013).

糖基化疾病，通常指先天性糖基化障碍（CDG），是一种罕见的遗传性疾病，其特征为核苷酸糖的生物合成和转运、糖基转移事件及囊泡运输的缺陷。大多数CDG导致神经系统损害，其严重程度从严重的心理运动迟缓至轻微的智力障碍不等。N-糖基化缺陷是CDG的主要病因（Marquardt & Denecke 2003，Grunewald et al. 2002，Hennet 2012，Goreta et al. 2012），可以通过血浆转铁蛋白的特征性异常等电聚焦谱进行识别（Jaeken et al. 1984，Stibler & Jaeken 1990）。近年来，O-糖基化、氨基糖聚糖和糖脂代谢的紊乱被发现，与N-糖基化一起，构成了糖类生物合成障碍的主要受影响途径（Freeze 2006，Jaeken 2011）。此外，本节还描述了与介导糖基化前体生物合成的酶相关的糖基化疾病。随着此类疾病的数量增加，命名学已得到简化，现在，突变基因的名称后跟随CDG的缩写（Jaeken et al. 2009）。迄今为止，大多数类型的CDG尚无有效治疗方法（Thiel & Korner 2013）。