Carbohydrate‐deficient Glycoprotein Syndrome Type II

Carbohydrate‐deficient glycoprotein syndromes (CDGS) are a family of multisystemic congenital diseases resulting in underglycosylated glycoproteins, suggesting defective N‐glycan assembly. Fibroblast extracts from two patients with a recently described variant of this disease (CDGS type II) have previously been shown to have over 98% reduced activity of UDP‐GlcNAc:α‐6– d ‐mannoside β‐1,2‐ N ‐acetylglucos‐aminyltransferase II [GlcNAc‐TII; Jaeken, J., Schachter, H., Carchon, H., De Cock, P., Coddeville, B. & Spik, G. (1994) Arch. Dis. Childhood 71 , 123–127]. We show in this paper that mononuclear cell extracts from one of these CDGS type‐II patients have no detectable GlcNAc‐TII activity and that similar extracts from 12 blood relatives of the patient, including his father, mother and brother, have GlcNAc‐TII levels 32–67% that of normal levels (average 50.1%±10.7% SD), consistent with an autosomal recessive disease. The poly( N ‐acetyllactosamine) content of erythrocyte membrane glycoproteins bands 3 and 4.5 of this CDGS patient were estimated, by tomato lectin blotting, to be reduced by 50% relative to samples obtained from blood relatives and normal controls. Similar to patients with hereditary erythroblastic multinuclearity with a positive acidified‐serum lysis test (HEMPAS), erythrocyte membrane glycoproteins in the CDGS patient have increased reactivities with concanavalin A, demonstrating the presence of hybrid or oligomannose carbohydrate structures. However, bands 3 and 4.5 in HEMPAS erythrocytes have almost complete lack of poly( N ‐acetyllactosamine). Furthermore, CDGS type‐II patients have a totally different clinical presentation and their erythrocytes do not show the serology typical of HEMPAS, suggesting that the genetic lesions responsible for these two diseases are possibly different.