title: The use of galactosylceramides with uniform fatty acids as substrates in the diagnosis and carrier detection of Krabbe disease.
abstract: Cerebroside-beta-galactosidase (galactosylceramidase EC 3.2.1.4.6) activity was studied using galactosylceramides of uniform fatty acid composition. The highest activity and the best discrimination between patients with Krabbe disease and controls were found with N-nervonoylgalactosylsphingosine (C 24: 1-cerebroside). As a general rule cerebrosides with a monoenoic fatty acid gave higher activity and better discrimination than the corresponding cerebroside with a saturated fatty acid, the differences being largest for the cerebrosides with the longest fatty acids. In two methods the C 24: 1 cerebroside was used as substrate in the assay of the cerebroside-beta-galactosidase activity in leukocytes from 12 Krabbe patients, 14 parents and 22 controls. In a third method lactosylceramide prepared from mammalian brain gangliosides was used as substrate. With all three methods the residual activity in the leukocytes of the Krabbe patients did not exceed 5%, there was no tendency for overlap between the activities of the patients and those of the obligate carriers, and the values of half the carriers fell within the range for the controls.
mesh_terms: D000328:Adult; D002554:Cerebrosides / Q000378:metabolism*; D005260:Female; D005696:Galactosidases / Q000097:blood*; D005698:Galactosylceramidase / Q000097:blood*; D005699:Galactosylceramides / Q000378:metabolism*; D006580:Genetic Carrier Screening / Q000379:methods*; D006801:Humans; D007223:Infant; D007790:Lactosylceramides / Q000378:metabolism; D007962:Leukocytes / Q000201:enzymology; D007965:Leukodystrophy, Globoid Cell / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D002554:Cerebrosides; D005699:Galactosylceramides; D007790:Lactosylceramides; C036570:N-nervonylgalactosylsphingosine; D005696:Galactosidases; D005698:Galactosylceramidase