Gargoylism: hydrolysis of β-galactosides and tissue accumulation of galactose- and mannose-containing compounds

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Abstract

The sugars present in hydrolyzed extracts of human liver and brain were analyzed by gasliquid chromatography after conversion to their alditol acetates. The samples analyzed were obtained from control subjects, patients with gargoylism, and patients with a few other kinds of storage disorders. Accumulation of galactose was demonstrated in the liver and the brain of two patients with gargoylism, and in the liver samples, high levels of mannose were found too. We also studied the hydrolysis of a number of galactosides by homogenates from different tissues in the control subjects and in the patients. Separation methods and kinetic studies demonstrated the presence in normal human tissues of two different β-galactosidases, which we call enzyme A and enzyme B, respectively. Enzyme A hydrolyzed all the β-galactosides tested. Enzyme B hydrolyzed the synthetic substrates tested (4-methylumbelliferyl-, p-nitrophenyl-, o-nitrophenyl-, and phenyl-β-galactoside) but not the natural substrates tested (ceramide-β-galactoside, ceramide lactoside, transferrin glycopeptide, and keratan sulfate). Enzyme B also exerted β-glucosidase activity. In various tissues from patients with gargoylism, deficiency of β-galactosidase A could be demonstrated.

Authors

Björn Hultberg, Per-Arne Öckerman, Arne Dahlqvist