Glycolipid Metabolism in the Canine form of Globoid Cell Leukodystrophy
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The underlying cause of globoid cell leukodystrophy (Krabbe’s disease) is a genetic deficiency of galactosylceramide α-galactosidase (galactosylceramidase, E.C. 126.96.36.199) which normally degrades galactosylceramide (21,22). In principle, the disease belongs to the so-called sphingolipidoses in which acidic lysosomal hydrolases are genetically deficient resulting in abnormal accumulation of sphingolipids specific in respective disorders. Unlike in other sphingolipidoses, abnormal accumulation of galactosylceramide does not occur in globoid cell leukodystrophy despite the block in its degradative pathway (22, 26). The only logical explanation for this unusual phenomenon appears to be that, sometime along the course of the disease, biosynthesis of galactosylceramide is terminated. Galactosylceramide is highly concentrated in the myelin sheath which is a specialized extension of the Oligodendroglial plasma membrane. It is, therefore, reasonable to assume that the Oligodendroglial cell is the major site of galactosylceramide biosynthesis in the brain. Since early and almost complete destruction of Oligodendroglia is one of the characteristic morphological features of the disease, cessation of galactosylceramide biosynthesis may merely be a secondary result of the abnormal histology. However, it is also possible that biosynthetic abnormality may precede death of Oligodendroglia, both due to the same as yet unidentified pathogenetic mechanism.
KeywordsWhite Matter Total Lipid Myelin Sheath Total Lipid Fraction Globoid Cell Leukodystrophy
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