Abstract

A rapidly fatal neurovisceral storage disease was discovered in both male and female offspring of clinically normal Nubian goats. Microscopic examination of fixed tissues revealed extensive demyelination and ubiquitous distribution of lysosomal storage vacuoles containing dispersed floccular material and membranous fragments. Urine was found to contain elevated levels of both mannose and N-acetylglucosamine, suggestive of an oligosaccharide storage disease. Brain was found to contain 2.2 mumol/g of a trisaccharide Man(beta 1-4)GlcNAc(beta 1-4)GlcNAc; (Jones, M. Z., and Laine, R. A. (1980) Fed. Proc. 39, 2521 and Jones, M. Z., and Laine, R. A. (1981) J. Biol. Chem. 256, 5181-5184). A profound deficiency of beta-D-mannosidase activity was found in a number of tissues from affected goats; obligate heterozygotes showed a partial enzyme deficiency. Other lysosomal hydrolase activities were normal or elevated over normal, including alpha-D-mannosidase, confirming that this was a hitherto undescribed inborn error of glycoprotein catabolism.