Congenital disorders of glycosylation (CDG) constitute an ever-growing group of genetic diseases affecting the glycosylation of proteins. CDG individuals usually present with severe multisystem disorders. MAN1B1-CDG is a CDG with nonspecific clinical symptoms such as intellectual deficiency and developmental delay. Although up to 40 affected individuals were described so far, its final diagnosis is not straightforward using common biochemical methods due to the trace-level accumulation of defective glycan structures. In this study, we present three unreported MAN1B1-CDG individuals and propose a decision tree to reach diagnosis using a panel of techniques ranging from exome sequencing to gel electrophoresis and mass spectrometry. The occurrence of MAN1B1-CDG in patients showing unexplained intellectual disability and development delay, as well as a particular transferrin glycosylation profile, can be ascertained notably using matrix assisted laser desorption/ionization – time of flight (MALDI-TOF) mass spectrometry analysis of endo-β-acetylglucosaminidase H-released serum N-glycans. In addition to reporting new pathogenic variants and additional clinical signs such as hypersialorrhea, we highlight particular biochemical features of MAN1B1-CDG with potential glycoprotein-specific glycosylation defects.

先天性糖基化障碍 (CDG) 是一组不断增长的影响蛋白质糖基化的遗传疾病。CDG 个体通常表现为严重的多系统疾病。MAN1B1-CDG 是一种具有非特异性临床症状的 CDG，如智力缺陷和发育迟缓。尽管到目前为止已描述了多达 40 名受影响的个体，但由于缺陷聚糖结构的痕量积累，使用常见的生化方法对其进行最终诊断并不容易。在这项研究中，我们展示了三个未报告的 MAN1B1-CDG 个体，并提出了一个决策树，以使用从外显子组测序到凝胶电泳和质谱法的一系列技术来实现诊断。MAN1B1-CDG在出现不明原因智力障碍和发育迟缓的患者中的发生，内-β-乙酰氨基葡萄糖苷酶 H 释放的血清 N-聚糖。除了报告新的致病变异和额外的临床症状（如唾液过多）外，我们还强调了具有潜在糖蛋白特异性糖基化缺陷的 MAN1B1-CDG 的特定生化特征。