Pathochemistry, pathogenesis and enzyme replacement in multiple-sulfatase deficiency.
Multiple-sulfatase deficiency (MSD) is now considered to be heterogeneous and could be classified into three or four clinical phenotypes according to the onset of the disease: neonatal, late infantile, juvenile and possibly adult type. Neonatal-type MSD shows severe clinical involvement and practically no arylsulfatase A, B and C activities in cultured skin fibroblasts. Furthermore, arylsulfatase A activity in neonatal-type MSD was not enhanced by the addition of thiosulfate. Therefore, it is distinct from late infantile-type MSD. The degradation of 14C-sulfatide can occur in MSD-cultured skin fibroblasts and was much higher than in late infantile-type MLD. The addition of thiol protease such as leupeptin to cultured MSD skin fibroblasts enhanced arylsulfatase A activity as well as the degradation of 14C-sulfatide. This suggests that the decreased activities of arylsulfatase A is due to an acceleration of the enzyme degradation. Enzyme replacement by the addition of arylsulfatases of different sources (human liver, brain, fungus) was carried out in cultured MSD skin fibroblasts. Human enzymes of arylsulfatase A and B were mostly taken up by MSD cells rather than those of fungus origin. By the exposure to leukocytes to cultured skin fibroblasts, MSD cells corrected arylsulfatase A and B activities.
D000293:Adolescent; D002478:Cells, Cultured; D002553:Cerebroside-Sulfatase / Q000378:metabolism; D002648:Child; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D007962:Leukocytes / Q000502:physiology; D011480:Protease Inhibitors / Q000494:pharmacology; D012867:Skin / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D013429:Sulfatases / Q000172:deficiency*; D013433:Sulfoglycosphingolipids / Q000378:metabolism; D013885:Thiosulfates / Q000494:pharmacology
D011480:Protease Inhibitors; D013433:Sulfoglycosphingolipids; D013885:Thiosulfates; D013429:Sulfatases; D002553:Cerebroside-Sulfatase