ISOFORMS AND LEVELS OF TRANSFERRIN, ANTITHROMBIN, ALPHA(1)-ANTITRYPSIN AND THYROXINE-BINDING GLOBULIN IN 48 PATIENTS WITH CARBOHYDRATE-DEFICIENT GLYCOPROTEIN SYNDROME TYPE-I

Carbohydrate-deficient glycoprotein syndrome type I(CDGS I) is an auto somal recessive disease with multiple organ manifestations. The diagno stic biochemical marker has been typical carbohydrate-deficient isofor ms of transferrin (Tf). Many other glycoproteins in blood may show sim ilar defects, but have not been systematically studied before. Forty-e ight CDGS I patients and 22 controls were examined for total concentra tions and isoform distribution of Tf, antithrombin (AT), alpha(1)-anti trypsin (alpha(1)-AT) and thyroxine-binding globulin (TBG), and for th e level of carbohydrate-deficient transferrin (CDT). The absolute valu es varied with age. The most frequent persistent quantitative changes were reduced levels of AT (97%) and elevated CDT values (100%). Isofor ms lacking one to eight of four to eight possible sialic acid residues were found in AT, TBG and Tf in all cases, with variable intensity an d frequency, and in all except one patient in alpha(1)-AT. The isoform changes were most constant and pronounced in Tf. The other three glyc oproteins showed more abnormal heterogeneity in the youngest than in t he older patients. The results indicated that the biochemical defect s tabilizes with age, and suggested partial hypoglycosylation rather tha n non-glycosylation of these glycoproteins. Analysis of Tf isoforms is still the safest diagnostic marker of CDGS I from full-term birth and over the ages.