[Pathophysiology of sulfatide metabolism in metachromatic leukodystrophy].
Metachromatic leucodystrophies (MLD) comprise a small group of heredodegenerative disorders of the nervous system. Deficiency of sulfatide-sulfatase or arylsulfatase A is the common defect in all forms of MLD leading to lysosomal sulfatide storage in the nervous tissue and in the kidney. On the basis of animal experiments, experiments with cultured fibroblasts of the patients as well as ultrastructural studies in a case of prenatal MLD, the following pathomechanism is proposed: 1. Lysosomal degradation of a large portion newly synthetised sulfatide normally regulating the net synthesis and incorporation of sulfatide into myelin, causes early accumulation of sulfatide in lysosomes of myelinating cells and in neurons in the genetic deficiency of arylsulfatase A. 2. Early accumulation of sulfatide does not lead to disturbance in myelination. Demyelination occurs possibly by storage of a cytotoxic compound, psychosin sulfate, also a substrate for the missing enzyme. Prevention of MLD is possible by prenatal diagnosis of arylsulfatase A deficiency in cultured amniotic cells. Enzyme substitution of the missing arylsulfatase A is possible by exogenous uptake of the enzyme in cultured fibroblasts. Thereby the defect of sulfatide degradation can be corrected. Although principles of enzyme substitution have been demonstrated, the problems of treating patients with MLD with arylsulfatase A infusions have yet to be overcome.
D000818:Animals; D002478:Cells, Cultured; D002553:Cerebroside-Sulfatase / Q000172:deficiency; D006801:Humans; D007668:Kidney / Q000378:metabolism; D007966:Leukodystrophy, Metachromatic / Q000175:diagnosis / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D009186:Myelin Sheath / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism; D011296:Prenatal Diagnosis; D011609:Psychosine / Q000378:metabolism; D012583:Schwann Cells / Q000378:metabolism; D013433:Sulfoglycosphingolipids / Q000378:metabolism*
D013433:Sulfoglycosphingolipids; D011609:Psychosine; D002553:Cerebroside-Sulfatase
Pathophysiologie des Sulfatidmetabolismus bei metachromatischen Leukodystrophien.