A CASE OF THE CARBOHYDRATE-DEFICIENT GLYCOPROTEIN SYNDROME TYPE-1 (CDGS TYPE-1) WITH NORMAL PHOSPHOMANNOMUTASE ACTIVITY

The carbohydrate-deficient glycoprotein syndrome (CDGS) is a group of disorders characterized biochemically by abnormal glycosylation of ser um and cellular glycoproteins. It has been classified into four forms on the basis of the isoelectric focusing pattern of serum transferrin and differences in clinical presentation. A deficiency of phosphomanno mutase (PMM) has been reported in most patients with type 1. Seven of our eight CDGS patients, classified clinically as type 1, were shown t o have a deficiency of phosphomannomutase in their fibroblast or lymph oblastoid cells (0.04-0.2 nmol/min per mg, compared with a control ran ge of 1.0-2.1 nmol/min per mg). The eighth patient, who had many clini cal features of the severe neonatal form of CDGS type 1. bur lacked de finite signs of CNS and ocular involvement, had a normal phosphomannom utase activity in his fibroblasts. There were approximately equal amou nts of disialo- and tetrasialotransferrin and only a trace amount of a sialotransferrin in the serum and ascitic fluid of this patient. The d isialo- and tetrasialotransferrin isoforms were purified by ion-exchan ge chromatography and analysed by SDS-PAGE. The disialotransferrin had a lower molecular mass than the tetrasialotransferrin, consistent wit h the absence of an N-linked glycan. The N-linked glycans released enz ymically from both isoforms consisted exclusively of disialylated bian tennary chains, suggesting that disialotransferrin results from underg lycosylation, as in the PMM-deficient CDGS type 1 patients. It is conc luded that the clinical and biochemical phenotype in CDGS type 1 call result from more than one basic defect.