A new variant of mannosidosis with increased residual enzymatic activity and mild clinical manifestation.
A partial deficiency of alpha-mannosidase was found in cultured skin fibroblasts, serum, and extracts of leukoytes in two siblings with mild mental retardation, delayed speech, a suggestion of coarse or full facies, and limited mobility of the large joints. All other lysosomal enzymes tested were within the normal range. Their father demonstrated intermediate alpha-mannosidase activity. The addition of 2 mM Zn++ caused a 40% increase of the alpha-mannosidase activity in cell extracts of both patients and control subjects. pH profiles and Cellogel electrophoresis of the patients' cells indicated 20% residual activity of the acidic alpha-mannosidase isoenzyme (pH optimum at 4.0), whereas the activity of the isozyme with pH optimum of 6.0 was normal. Increasing substrate concentration (1--10 mM) demonstrated a 4 to 5-fold increase in the apparent Km of the acidic alpha-mannosidase in the patients' fibroblasts. This residual activity, however, was apparently not sufficient for the normal catabolism of mannose-containing molecules, since electron microscopic examination of the cultured fibroblasts demonstrated numerous lysosomal storage bodies.
D001192:Arylsulfatases / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D005347:Fibroblasts / Q000201:enzymology / Q000648:ultrastructure; D005696:Galactosidases / Q000378:metabolism; D005966:Glucuronidase / Q000378:metabolism; D006026:Glycoside Hydrolases / Q000378:metabolism*; D006596:Hexosaminidases / Q000378:metabolism; D006801:Humans; D007962:Leukocytes / Q000201:enzymology; D008297:Male; D008361:Mannosidases / Q000097:blood / Q000172:deficiency* / Q000378:metabolism; D010375:Pedigree; D005644:alpha-L-Fucosidase / Q000378:metabolism
D001192:Arylsulfatases; D005696:Galactosidases; D006026:Glycoside Hydrolases; D006596:Hexosaminidases; D008361:Mannosidases; D005966:Glucuronidase; D005644:alpha-L-Fucosidase