Chemical pathology of krabbe's disease. IV. Studies of galactosylceramide and lactosylceramide BETA-galactosidases in brain, white blood cells and aminotic fluid cells.

Galactosylceramide beta-galactosidase and lactosylceramide beta-galactosidase activities were investigated in normal human brain, leu-kocytes and amniotic fluid cells. The enzymatic assays were performed on brains from 11 patients with Krabbe's disease, on leukocytes from 16 patients and 18 obligate heterozygotes, and on amniotic fluid cells from 9 foetuses at risk. The brain enzyme was solubilized from a 900 g-100000 g pellet. With this enzyme preparation a profound deficiency of galactosylceramide beta-galactosidase activity in brain, approximately 1% of that in age-matched controls was shown. The lactosylceramide beta-galactosidase activity of brain was also strongly reduced, but not to the same extent as the other beta-galactosidase. Galactosylceramide beta-galactosidase activity in leukocytes from patients with Krabbe's disease was generally less than 5% of that in age-matched controls and there was no overlap between the patients and the obligate heterozygotes. Carrier detection by the leukocyte enzyme was, however, not possible because of considerable overlap between heterozygotes and normal controls. The lactosylceramide beta-galactosidase activity was only moderately reduced in leukocytes, but strongly reduced in cerebral tissue from patients with Krabbe's disease. The changes in the glycolipid pattern of cerebral tissue, recently described by us in patients with Krabbe's disease, offers an explanation to the serious glycolipid beta-galactosidase deficiency in CNS.