title: Biochemical aspects of globoid and metachromatic leukodystrophies.
abstract: Galactosylceramides and sulfogalactosylceramides are characteristic lipids of the myelin sheath. Two genetically determined leukodystrophies are caused by an inability to enzymically hydrolyze these glycolipids. Thus, a deficiency of galactocerebroside beta-galactosidase results in globoid cell leukodystrophy, whereas a reduced activity of arylsulfatase A is responsible for metachromatic leukodystrophy. Besides these disorders, deficiencies of arylsulfatases A, B, C, and other sulfatases have been shown in a distinct condition called "multiple sulfatase deficiency." All of these disorders are fatal and are characterized by marked demyelination and severe mental retardation. The cause of this demyelination is not known. However, cytotoxic galactosylsphingosine and sulfogalactosylsphingosine have been suggested as the agents responsible for this demyelination. Recent immunological studies have also shown that patients with globoid and metachromatic leukodystrophies contain a mutant galactocerebroside beta-galactosidase and arylsulfatase A, respectively. The mutant enzymes have different kinetic properties compared to the enzymes from normal subjects. However, they can cross-react with antibodies to these enzymes. Since partially purified preparations of galactocerebroside beta-galactosidase and homogeneous arylsulfatase A are now available, the possibility of enzyme replacement therapy in globoid and metachromatic leukodystrophies is discussed.
mesh_terms: D000818:Animals; D002553:Cerebroside-Sulfatase / Q000172:deficiency / Q000235:genetics / Q000627:therapeutic use; D055598:Chemical Phenomena; D002621:Chemistry; D003711:Demyelinating Diseases / Q000209:etiology; D004195:Disease Models, Animal; D005698:Galactosylceramidase / Q000235:genetics; D006801:Humans; D007965:Leukodystrophy, Globoid Cell / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism*; D007966:Leukodystrophy, Metachromatic / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism*; D009154:Mutation; D009186:Myelin Sheath / Q000378:metabolism; D013429:Sulfatases / Q000172:deficiency
chemical_list: D013429:Sulfatases; D002553:Cerebroside-Sulfatase; D005698:Galactosylceramidase