Studies of a synthetic substrate in canine globoid cell leukodystrophy

Gal et al. ((1977) Clin. Chim. Acta 77, 53-59) reported the use of a new synthetic substrate, 2-hexadecanoylamino-4-nitrophenyl-β-D-galactopyranoside for the diagnosis of human globoid cell leukodystrophy. Assay of β-galactosidase in brain homogenates from normal, carrier, and globoid cell leukodystrophy-affected dogs utilizing this new substrate demonstrated overlapping activities. Instead of reflecting specific D-galactosyl-N-acylsphingosine galactohydrolase (EC 3.2.1.46), the 2-hexadecanoylamino-4-nitrophenyl-β-D-galactopyranoside β-galactosidase activity in canine brain is highly correlated with nonspecific 4-methylumbelliferyl β-galactosidase. Optimization of the 2-hexadecanoylamino-4-nitrophenyl-β-D-galactopyranoside assay system for canine brain and the use of varying concentrations of taurocholate or taurodeoxycholate in the assay mixture did not alter the lack of specificity. These results indicate a significant difference in the nature of the underlying defect in galactosylceramide β-galactosidase in canine globoid cell leukodystrophy compared to human globoid cell leukodystrophy.