Jos Jansen

124 Chapter 5 that the QTOF-MS analysis ruled out abnormal glycosylation due to a defect in V-ATPase-CDG. However, we cannot completely exclude another, possibly novel, CDG. Another limitation of our study is the high percentage of exclusion of samples resulting from low abundance of serumTF in the samples. A possible explanation could be that low serum TF is associated with cirrhosis.(37, 38). Additionally, the effect of long term storage on stability of TF is unknown. Recommendations Differentiating primary from secondary glycosylation defects in patients with liver dysfunction can be challenging. Previously analysis of total plasmaN-glycans suggested that hyperfucosylation was increased in a single liver disease patient but not in primary CDG.(39) This study expands these findings to a large patient group and thus transferrin hyperfucosylation pattern could guide clinicians in decision making. Our current research exposes caveats in tIEF as a primary diagnostic step. We show that 26% of tiEF samples were abnormal, but these samples did not show a clear type 2 CDG pattern upon QTOF-MS analysis. An important message is that tIEF screening can be false positive because of liver dysfunction. We suggest caution when interpreting tIEF result in patients with a suspected CDG and liver disease and recommend maintaining a low-threshold to use advanced glycoanalytic methods, preferably in an expertise center. A clear hyperfucosylated pattern is more suggestive for a secondary cause and loss of galactose more suggestive for a primary glycosylation defect. When only sialylation is decreased, we suggest a repeat sample to rule out the involvement of exogeneous sialidase and a critical review of the phenotype to rule out a CDG with known hyposialylation.