CARBOHYDRATE-DEFICIENT GLYCOPROTEIN SYNDROME TYPE-II - AN AUTOSOMAL RECESSIVE N-ACETYLGLUCOSAMINYLTRANSFERASE-II DEFICIENCY DIFFERENT FROM TYPICAL HEREDITARY ERYTHROBLASTIC MULTINUCLEARITY, WITH A POSITIVE ACIDIFIED-SERUM LYSIS TEST (HEMPAS)

Carbohydrate-deficient glycoprotein syndromes (CDGS) are a family of m ultisystemic congenital diseases resulting in underglycosylated glycop roteins, suggesting defective N-glycan assembly. Fibroblast extracts f rom two patients with a recently described variant of this disease (CD GS type II) have previously been shown to have over 98% reduced activi ty of UDP-GlcNAc:alpha-6-D-mannoside beta-1,2-N-acetylglucosaminyltran sferase II [GlcNAc-TII; Jaeken, J., Schachter, H., Carchon, H., De Coc k, P., Coddeville, B. and Spik, G. (1994) Arch. Dis. Childhood 71, 123 -127]. We show in this paper that mononuclear cell extracts from one o f these CDGS type-II patients have no detectable GlcNAc-TII activity a nd that similar extracts from 12 blood relatives of the patient, inclu ding his father, mother and brother, have GlcNAc-TII levels 32-67% tha t of normal levels (average 50.1% +/- 10.7% SD), consistent with an au tosomal recessive disease. The poly(N-acetyllactosamine) content of er ythrocyte membrane glycoproteins bands 3 and 4.5 of this CDGS patient were estimated, by tomato lectin blotting, to be reduced by 50% relati ve to samples obtained from blood relatives and normal controls. Simil ar to patients with hereditary erythroblastic multinuclearity with a p ositive acidified-serum lysis test (HEMPAS), erythrocyte membrane glyc oproteins in the CDGS patient have increased reactivities with concana valin A, demonstrating the presence of hybrid or oligomannose carbohyd rate structures. However, bands 3 and 4.5 in HEMPAS erythrocytes have almost complete lack of poly(N-acetyllactosamine). Furthermore, CDGS t ype-II patients have a totally different clinical presentation and the ir erythrocytes do not show the serology typical of HEMPAS, suggesting that the genetic lesions responsible for these two diseases are possi bly different.