Chemical pathology of Krabbe's disease. III. Ceramide-hexosides and gangliosides of brain.

Neutral ceramide-hexosides and gangliosides in cerebral cortex and white matter of children who had died in Krabbe's disease were quantitatively isolated and characterized. The concentrations of galactosylceramides; lactosylceramides and glucosylceramides were normal or slightly increased in cerebral cortex, but all the three glycolipids were diminsihed in white matter, particularly the galactosylceramides. More complex ceramide-hexosides, globotriose, globotetraose and blood-group substance H, present in trace amounts in normal brain, were much more abundant in cerebral cortex and especially in white matter of brains affected by Krabbe's disease. The composition of the ceramide portion suggested that these glycolipids as well as a portion of the lactosylceramides and glucosylceramides were structural components of the globoid cell. The ganglioside distribution was severely altered. GD1a and GM1 were severely reduced in cerebral cortex and white matter, while GD1b and GT1 were slightly decreased in cerebral cortex, but increased in white matter. Normally minor brain gangliosides metabolically related to GD1b and GT1, i.e. GD2, GD3 and GM3, were strongly increased in cerebral cortex and in white matter. For the first time galactosylsphingosine (psychosine) was demonstrated in normal infant brain. In cerebral tissue affected by Krabbe's disease the concentration of psychosine was at least 10 times higher. The large increase in this cytotoxic substance might be the primary lesion in Krabbe's disease.