Prenatal diagnosis of GM2 gangliosidosis with high residual hexosaminidase A activity (variant B1; pseudo AB variant).
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.
Conzelmann
E
E
Nehrkorn
H
H
Kytzia
H J
HJ
Sandhoff
K
K
Macek
M
M
Lehovský
M
M
Elleder
M
M
Jirásek
A
A
Kobilková
J
J
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
D049289:G(M2) Activator Protein; C028960:GM2-N-acetyl-beta-D-galactosaminidase; D006596:Hexosaminidases; D054818:Hexosaminidase A; D001619:beta-N-Acetylhexosaminidases