title: Complementation of arylsulfatase A in somatic hybrids of metachromatic leukodystrophy and multiple sulfatase deficiency disorder fibroblasts.
abstract: Metachromatic leukodystrophy and multiple sulfatase deficiency disorder are severe neurodegenerative diseases inherited as separate autosomal recessive traits. Arylsulfatase A (aryl-sulfate sulfohydrolase, EC 3.1.6.1) activity is deficient in both diseases but in multiple sulfatase deficiency disorder, activities of arylsulfatases B and C and other sulfatases are also reported to be reduced. Somatic hybrid cell clones produced by fusing cultured fibroblasts from patients with these diseases were isolated by a nonselective technique based on unit-gravity sedimentation. Arylsulfatase A activity was restored in these hybrids. The complemented enzyme resembled the normal arylsulfatase A in heat stability, pH optimum, Km, electrophoretic mobility, and immunologic reactivity. Because a structurally normal enzyme can be restored in a hybrid only though intergenic complementation, these results indicate that the mutations responsible for the deficiency of arylsulfatase A activity in metachromatic leukodystrophy and multiple sulfatase deficiency disorder are nonallelic and that at least two genetic loci control the expression of arylsulfatase A activity in the human genome. Furthermore, arylsulfatase C activity was also restored to normal in the hybrids, indicating that a common sulfatase inhibitor is not the cause of the multiple sulfatse deficiency.
mesh_terms: D002478:Cells, Cultured; D002553:Cerebroside-Sulfatase / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D005816:Genetic Complementation Test; D006358:Hot Temperature; D006801:Humans; D006822:Hybrid Cells / Q000201:enzymology; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D007966:Leukodystrophy, Metachromatic / Q000201:enzymology* / Q000235:genetics; D013429:Sulfatases / Q000172:deficiency*
chemical_list: D013429:Sulfatases; D002553:Cerebroside-Sulfatase