Galactosialidosis: molecular heterogeneity among distinct clinical phenotypes.
The lysosomal storage disorder galactosialidosis has been recognized as a distinct genetic and biochemical entity, associated with a combined beta-galactosidase and neuraminidase deficiency that is due to the lack of a 32-kilodalton (kDa) glycoprotein. The molecular basis of different clinical variants of galactosialidosis has been investigated. In the early-infantile form, the synthesis of the 52-kDa precursor of the 32-kDa "protective protein" is markedly reduced and the absence of the latter protein explains the severe neuraminidase deficiency. In the juvenile-adult form, there is relatively more 52-kDa precursor but no 32-kDa protein can be detected. Cells from the late-infantile form have in comparison with controls, besides a small amount of the 32-kDa glycoprotein, an accumulation of the 52-kDa precursor. Apparently, this protein is genetically altered in such a way that its further processing is impaired. Furthermore, in this mutant, the residual neuraminidase activity is stimulated four- to sixfold upon leupeptin treatment together with an increase of the 32-kDa glycoprotein.
Palmeri
S
S
Hoogeveen
A T
AT
Verheijen
F W
FW
Galjaard
H
H
D000328:Adult; D002478:Cells, Cultured; D011232:Chemical Precipitation; D004591:Electrophoresis, Polyacrylamide Gel; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism; D005696:Galactosidases / Q000172:deficiency*; D014644:Genetic Variation; D006023:Glycoproteins / Q000096:biosynthesis; D006801:Humans; D007223:Infant; D008247:Lysosomes / Q000201:enzymology; D008970:Molecular Weight; D009154:Mutation; D009439:Neuraminidase / Q000172:deficiency* / Q000235:genetics; D010641:Phenotype; D001616:beta-Galactosidase / Q000172:deficiency* / Q000235:genetics
D006023:Glycoproteins; D005696:Galactosidases; D009439:Neuraminidase; D001616:beta-Galactosidase