Globoid cell leukodystrophy (Krabbe's disease). Metabolic studies with cultured fibroblasts

Metabolism of tritium-labelled galactosylceramide and lactosylceramide added to the culture medium was examined in cultured skin fibroblasts from 4 patients with globoid cell leukodystrophy (GLD) and 4 control individuals. The uptake of [3H]galactosylceramide and [3H]lactosylceramide by the fibroblasts continued actively at least up to 3 days. Approximately 30--40% of the galactosylceramide, which had been taken up, was released subsequently from the cells in a 4-day period, whereas only 10% of lactosylceramide was released during the same period. The GLD fibroblasts showed no abnormality in the kinetics of the uptake and in the release of these glycosphingolipids which are natural substrates of the beta-galactosidase genetically deficient in the disorder. This finding differs from that reported for fibroblasts from patients with metachromatic leukodystrophy, which showed abnormal accumulation and retention of sulfatide added to the culture media. However, degradation of added galactosylceramide to [3H]galactose by the GLD fibroblasts was only 25% of the control cells, while lactosylceramide was degraded at 70% of the normal rate. These findings are consistent with the known substrate specificities of the two acidic beta-galactosidases in human tissues; galactosylceramide is hydrolyzed almost exclusively by galactosylceramidase, while lactosylceramide can be hydrolyzed by both galactosylceramidase and GM1-ganglioside beta-galactosidase.