Screening for abnormal glycosylation in a cohort of adult liver disease patients
Congenital Disorders of Glycosylation (CDG) are a rapidly expanding group of rare genetic defects in glycosylation. In a novel CDG subgroup of Vacuolar-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 deficiencies. 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, not indicative for a V-ATPase assembly factor defect. Advanced glycoanalytical techniques assist in the dissection of secondary and primary glycosylation defects. This article is protected by copyright. All rights reserved.
|Congenital Disorders of Glycosylation, end-stage liver disease, hyperfucosylation, N-glycosylation, V-ATPase assembly factor deficiencies|
|Journal of Inherited Metabolic Disease|
|Organisation||Department of Gastroenterology & Hepatology|
Jansen, J.C. (Jos C.), van Hoek, B, Metselaar, H.J, van den Berg, A.P, Zijlstra, F. (Fokje), Huijben, K, … Lefeber, D.J. (Dirk J.). (2020). Screening for abnormal glycosylation in a cohort of adult liver disease patients. Journal of Inherited Metabolic Disease. doi:10.1002/jimd.12273