Congenital disorders of glycosylation (CDG) are a rapidly expanding group of rare genetic defects in glycosylation. In a novel CDG subgroup of vacuolar‐ATPase (V‐ATPase) assembly defects, various degrees of hepatic injury have been described, including end‐stage liver disease. However, the CDG diagnostic workflow can be complex as liver disease per se may be associated with abnormal glycosylation. Therefore, we collected serum samples of patients with a wide range of liver pathology to study the performance and yield of two CDG screening methods. Our aim was to identify glycosylation patterns that could help to differentiate between primary and secondary glycosylation defects in liver disease. To this end, we analyzed serum samples of 1042 adult liver disease patients. This cohort consisted of 567 liver transplant candidates and 475 chronic liver disease patients. Our workflow consisted of screening for abnormal glycosylation by transferrin isoelectric focusing (tIEF), followed by in‐depth analysis of the abnormal samples with quadruple time‐of‐flight mass spectrometry (QTOF‐MS). Screening with tIEF resulted in identification of 247 (26%) abnormal samples. QTOF‐MS analysis of 110 of those did not reveal glycosylation abnormalities comparable with those seen in V‐ATPase assembly factor defects. However, two patients presented with isolated sialylation deficiency. Fucosylation was significantly increased in liver transplant candidates compared to healthy controls and patients with chronic liver disease. In conclusion, a significant percentage of patients with liver disease presented with abnormal CDG screening results. However, the glycosylation pattern was not indicative for a V‐ATPase assembly factor defect. Advanced glycoanalytical techniques assist in the dissection of secondary and primary glycosylation defects.

中文翻译：

---

在一组成人肝病患者中筛查异常糖基化。

先天性糖基化障碍 (CDG) 是一组迅速扩大的糖基化罕见遗传缺陷。在一个新的液泡-ATP酶（V-ATP酶）组装缺陷CDG亚组中，已经描述了不同程度的肝损伤，包括终末期肝病。然而，CDG 诊断工作流程可能很复杂，因为肝病本身可能与异常糖基化有关。因此，我们收集了多种肝脏病理患者的血清样本，以研究两种 CDG 筛查方法的性能和产量。我们的目标是确定糖基化模式，有助于区分肝病中的原发性和继发性糖基化缺陷。为此，我们分析了 1042 名成人肝病患者的血清样本。该队列由 567 名肝移植候选者和 475 名慢性肝病患者组成。我们的工作流程包括通过转铁蛋白等电聚焦 (tIEF) 筛查异常糖基化，然后使用四极杆飞行时间质谱 (QTOF-MS) 对异常样品进行深入分析。使用 tIEF 进行筛选后发现了 247 (26%) 个异常样本。其中 110 个的 QTOF-MS 分析没有显示出与 V-ATPase 组装因子缺陷中所见的糖基化异常相当。然而，两名患者表现出孤立的唾液酸化缺乏症。与健康对照和慢性肝病患者相比，肝移植候选者的岩藻糖基化显着增加。综上所述，很大比例的肝病患者出现异常的 CDG 筛查结果。然而，糖基化模式并不表示 V-ATPase 组装因子缺陷。先进的糖基分析技术有助于剖析二级和一级糖基化缺陷。