Inhibition of alpha-glucosidase in cattle by Castanospermum australe: an attempted phenocopy of Pompe's disease

Pompe's disease is characterised by an absence of lysosomal alpha-glucosidase, but this enzyme is also inhibited by Castanospermum australe seeds. Four calves were fed C. australe seeds at the rate of 0.15 g/kg body weight for periods from 1 to 4 days. Lymphocyte alpha-glucosidase activity was reduced by at least 90%, with the majority of inhibition occurring within 8 h of dosing. Several weeks elapsed before activity returned to normal. Significant inhibition of muscle alpha-glucosidase occurred and the ratio of plasma alpha-glucosidase activity measured at pH 5.6 relative to that at pH 3.7 was depressed. In an attempt to induce Pompe's disease, 2 calves were dosed with 1.2 g C. australe seed/kg body weight/day for 13 months. Lymphocyte and muscle alpha-glucosidase activities were markedly reduced over the entire period of feeding, but the animals showed no clinical signs of disease. Tissue cells were not vacuolated nor did they show any apparent accumulation of glycogen. Despite significant inhibition of alpha-glucosidase in skeletal and cardiac muscle, liver, kidney and brain, it is suggested that there was sufficient residual enzyme to prevent induction of a phenocopy of Pompe's disease.