title: Prenatal diagnosis of GM2 gangliosidosis with high residual hexosaminidase A activity (variant B1; pseudo AB variant).
abstract: A case of infantile GM2 gangliosidosis with high residual beta-hexosaminidase A activity toward the synthetic substrate 4-methylumbelliferyl-2-acetamido-2-deoxy-beta-D-glucopyranoside was diagnosed prenatally. Extracts from cultured amniotic fluid cells of the fetus had a hexosaminidase A activity of 27% of total hexosaminidase but were almost completely unable to degrade [3H]ganglioside GM2 (less than 0.5% of control values) when assayed in the presence of the natural activator protein. These results were confirmed by analyses of fetal muscle fibroblasts, liver, and brain. All tissues examined showed a profound deficiency of ganglioside GM2 galactosaminidase despite hexosaminidase A levels in the heterozygote range. In brain tissue, ganglioside GM2 content was elevated more than 4-fold. Hydrolysis of p-nitrophenyl glucosaminide-6-sulfate, a substrate specific for hexosaminidases A and S, by tissue extracts was also markedly reduced but the residual activities found (5% in liver, 12% in fibroblasts, and 16% in brain) were much higher than those with the physiological lipid substrate, ganglioside GM2.
authors.forename: E
authors.initials: E
authors.lastname: Conzelmann
authors.forename: H
authors.initials: H
authors.lastname: Nehrkorn
authors.forename: H J
authors.initials: HJ
authors.lastname: Kytzia
authors.forename: K
authors.initials: K
authors.lastname: Sandhoff
authors.forename: M
authors.initials: M
authors.lastname: Macek
authors.forename: M
authors.initials: M
authors.lastname: Lehovský
authors.forename: M
authors.initials: M
authors.lastname: Elleder
authors.forename: A
authors.initials: A
authors.lastname: Jirásek
authors.forename: J
authors.initials: J
authors.lastname: Kobilková
mesh_terms: D000649:Amniocentesis; D000653:Amniotic Fluid / Q000201:enzymology; D005260:Female; D005333:Fetus / Q000201:enzymology; D049289:G(M2) Activator Protein; D005733:Gangliosidoses / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics; D054818:Hexosaminidase A; D006596:Hexosaminidases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007223:Infant; D008297:Male; D011247:Pregnancy; D011296:Prenatal Diagnosis; D013661:Tay-Sachs Disease / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics; D001619:beta-N-Acetylhexosaminidases
chemical_list: D049289:G(M2) Activator Protein; C028960:GM2-N-acetyl-beta-D-galactosaminidase; D006596:Hexosaminidases; D054818:Hexosaminidase A; D001619:beta-N-Acetylhexosaminidases