title: 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).
abstract: 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:alpha-6-D-mannoside beta-1,2-N-acetylglucosaminyltransferase 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.
authors.affiliation: Department of Medicine, University of Toronto, Canada.
authors.forename: J H
authors.initials: JH
authors.lastname: Charuk
authors.forename: J
authors.initials: J
authors.lastname: Tan
authors.forename: M
authors.initials: M
authors.lastname: Bernardini
authors.forename: S
authors.initials: S
authors.lastname: Haddad
authors.forename: R A
authors.initials: RA
authors.lastname: Reithmeier
authors.forename: J
authors.initials: J
authors.lastname: Jaeken
authors.forename: H
authors.initials: H
authors.lastname: Schachter
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000742:Anemia, Dyserythropoietic, Congenital / Q000175:diagnosis*; D002240:Carbohydrate Sequence; D002648:Child; D002675:Child, Preschool; D003937:Diagnosis, Differential; D004910:Erythrocyte Membrane / Q000378:metabolism; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D037102:Lectins / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008361:Mannosidases / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D008661:Metabolism, Inborn Errors / Q000175:diagnosis* / Q000235:genetics; D008875:Middle Aged; D008969:Molecular Sequence Data; D017351:N-Acetylglucosaminyltransferases / Q000172:deficiency*; D010375:Pedigree; D013577:Syndrome
chemical_list: D037102:Lectins; D008562:Membrane Glycoproteins; D017351:N-Acetylglucosaminyltransferases; C063312:beta-1,3-galactosyl-0-glycosyl-glycoprotein beta-1,3-N-acetylglucosaminyltransferase; D008361:Mannosidases