Biochemical and histochemical analysis of lysosomal enzyme activities in caprine β-mannosidosis

Goats affected with β-mannosidosis, and autosomal recessive disease of glycoprotein catabolism, have deficient tissue and plasma levels of the lysosomal enzyme β-mannosidase. Pathological characteristics include cytoplasmic vacuolation in the nervous system and viscera, and myelin deficits that demonstrate regional variation. This study was designed to determine the correlation between β-mannosidase activity in normal animals and the severity of lesions in affected goats, and to assess the regional changes in lysosomal enzyme activity in specific regions and cell types in affected animals. Although enzyme activity in normal organs (kidney, thyroid, brain) is correlated in general with the accumulation of uncatabolized substrate and with the extent of vacuolation, this correlation does not extend to assessment of specific region of the central nervous system (CNS). In affected goats, the activities of α-mannosidase, α-fucosidase, and β-hexosaminidase are elevated to a greater extent in all CNS regions than in organs. The results suggest cell-specific, organ-specific, and enzyme-specific regulation of changes in lysosomal enzyme activity in the presence of metabolic perturbations, such as deficiency of β-mannosidase activity.