Jos Jansen

122 Chapter 5 19). Spontaneous normalization of the glycosylation profile has not yet been investigated for V-ATPase-CDG. However, spontaneous normalization of serum transaminases has been described with this condition. (4) We identified two patients with an abnormally high percentage of the isoform with loss of one sialic acid. The reason for this abnormal pattern remains unknown. Glycosylation defects in SLC35A1-CDG (OMIM 603585), a defect in the CMP-sialic acid transporter, show pure desialylation effects (15, 20). However, the phenotype of SLC35A1-CDG is mostly neurological with dysmorphic features, not hepatic. Also, the presence of bacterial sialidase in serum can lead to hyposialylation of TF. This has been described for Streptococcus pneumoniae- associated hemolytic ureum syndrome.(21). However, hemolytic uremic syndrome is primarily a disease of infancy and early childhood and the incidence in the adult population is extremely low. Another option is that these patients have an as yet unrecognized type of CDG. Our study design did not allow us to further investigate this as we did not have access to fresh plasma, fibroblasts or parental DNA to perform adequate genetic analyses and functional studies. Glycosylation defects in liver disease Desialylation has been mostly studied in the context of alcoholic liver disease. Indeed, the Carbohydrate Deficient Transferrin (CDT) test to identify chronic alcohol intake is based on desialylation of transferrin. Analysis of CDT in abstaining patients with various degrees of liver disease shows a correlation of high CDT percentages with the Child-Pugh score.(22) The pathophysiological mechanism behind alcohol-induced hypoglycosylation is not fully elucidated. Some studies suggest a primary ER defect (23, 24). Other studies suggest an effect on the Golgi apparatus.(25, 26). One study investigated gene expression of glycosylation genes in NASH but found mixed results with upregulation of ST6GAL2 and downregulation of ST6GAL1 .(11) Hyperfucosylation of liver derived proteins has been most extensively studied in hepatocellular carcinoma patients. (27-30) Indeed, fucosylated alpha-fetoprotein is an established disease marker for HCC in the setting of cirrhosis.(31) Here we