Krabbes Disease

Krabbe's disease, or globoid cell leukodystrophy, an autosomal recessive disorder chiefly of infants, is caused by a deficiency of the lysosomal enzyme galactosyl ceramidase, which degrades the cerebroside (galactosyl ceramide) to ceramide and galactose. The mutant gene is located on chromosome 14. The enzymatic failure leads to an accumulation of galactosylceramide in globoid cells and an accumulation of toxic galactosyl-sphingosine (psychosine) in the white matter and oligo-dendrocytes, which accounts for the myelin degeneration and oligodendroglial loss. Globoid cells in the demyelin-ated areas are the diagnostic features of the disease. These large mono- or multinucleated macrophages contain galactocerebrosides that stain strongly with PAS reagent and weakly for lipids. The globoid cells have a tendency to cluster, particularly around blood vessels (Fig. 9.12).

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