Jos Jansen

5 121 Screening for abnormal glycosylation in a cohort of adult liver disease patients Discussion In our retrospective analysis of a cohort of 1042 liver disease patients we found a significant percentage of patients with altered CDG screening results by serum transferrin isoelectric focusing. However, we did not find clear evidence for the presence of a CDG due to V-ATPase assembly factor defects. We found that hyperfucosylation is more pronounced in LTx patients compared to those with milder liver disease and healthy controls, thereby showing that high-resolution mass spectrometry aids the discrimination between secondary and primary glycosylation abnormalities in CDG screening. Screening for possible primary glycosylation defects Initial screening with tIEF resulted in identification of 247 (26%) , mostly mild, abnormal patterns. We did not identify a typical CDG type 1 pattern, which we anticipated, as to date there are no known type 1 CDG associated with a mild hepatic phenotype.(1) The majority of samples had an increase in the trisialo TF isoform. None had an increase of all isoforms, a feature of most type 2 CDG. However, based on these tIEF results we could not rule out a V-ATPase assembly factor deficiency as mild abnormalities have been described. QTOF-MS analysis did not confirmdesialylation as seen in tIEF and did not showpatterns compatible with type 1 CDG or V-ATPase assembly factor deficiencies. Similarly, no samples with loss of galactose were observed. Therefore, we conclude that our analysis did not identify novel patients with a V-ATPase assembly factor defect. A possible reason for this might be that prevalence is too low for detection within our cohort. The exact prevalence of the whole group of CDG is unknown but is estimated at 0.1 – 0.5 / 100.000 in Europe. This number is based on recent data from the European CDG network that estimated that there is a total number of 2500 recognized CDG patients in Europe. (1) However, these observations are based on patients with a multisystem phenotype. The discovery of the V-ATPase-CDG subgroup with a very mild hepatic phenotype could indicate that the prevalence is much higher. We speculated that this subgroup would be enriched in a population that covers the full spectrum of liver disease severity, but no cases were detected. Another reason might be that glycosylation defects of CDG patients who survive into adulthood can become milder, or even normalize, over time. (17-