J. Charlwood et al., A CASE OF THE CARBOHYDRATE-DEFICIENT GLYCOPROTEIN SYNDROME TYPE-1 (CDGS TYPE-1) WITH NORMAL PHOSPHOMANNOMUTASE ACTIVITY, Journal of inherited metabolic disease, 20(6), 1997, pp. 817-827
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.