Clinical and biochemical heterogeneity of globoid cell leukodystrophy.

The residual galactosylceramide beta-galactosidase activity in cultured skin fibroblasts from a child with late-onset globoid cell leukodystrophy (GLD) was distinctly different from that found in the typical infantile form of the disease. The residual enzyme activity and maximum velocity of the enzyme reaction were higher in this patient, while the Michaelis constant was similar in controls and in the two forms of GLD. The pH optimum of enzyme activity from the patient was similar to that of controls and a more acidic pH optimum was found in the infantile form. Cultured skin fibroblasts from the patient accumulated less [6(3)H]-galactosylceramide than did cells from the infantile form. These various biochemical measurements correlated well with the age of onset of the disease and suggest that different allelic mutations of the galactosylceramide beta-galactosidase locus are responsible for the different clinical forms of GLD.