MICROHETEROGENEITY OF SERUM GLYCOPROTEINS AND THEIR LIVER PRECURSORS IN PATIENTS WITH CARBOHYDRATE-DEFICIENT GLYCOPROTEIN SYNDROME TYPE-I -APPARENT DEFICIENCIES IN CLUSTERIN AND SERUM AMYLOID-P

Serum and liver protein patterns were studied, respectively, in 5 pati ents (serum) and 1 patient (liver) with carbohydrate-deficient glycopr otein syndrome (CDGS) type I by high-resolution two-dimensional electr ophoresis (2-DE) and sodium dodecyl sulfate-polyacrylamide gel electro phoresis (SDS-PAGE). The pattern of serum glycoproteins in all 5 patie nts presented abnormal trains of isoforms with decreased mass (delta m olecular weight 3000) and all showed a cathodal shift. Two-dimensional electrophoresis and SDS-PAGE mass analysis of transferrin, alpha 1-an titrypsin, haptoglobin beta-chain, and alpha 1-acid glycoprotein after neuraminidase and N-glycosidase F treatments demonstrated that the ad ditional trains of the isoforms found in CDGS type I contain homologou s species of Isoforms. Some of them still showed charge differences, a nd all still contained glycans except for transferrin, with some unusu al nonglycosylated isoforms, in addition, deficiencies in clusterin an d serum amyloid P, not described so far, have been found in all 5 pati ents. The two-dimensional pattern of immunodetected precursors of seru m proteins in liver cells from ii patient with CDGS showed abnormal lo w-mass precursors and the absence of the precursors normally found in controls. These results suggest that these abnormal precursors accumul ate during the early oligosaccharide processing of the nascent protein -bound oligosaccharides and that glycoprotein precursors undergo an al tered intracellular transport while the post-translational processing along the normal pathway is still apparently functioning in patients w ith CDGS.