Aspartylglycosaminuria: A generalized storage disease

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Abstract
Aspartylglycosaminuria (AGU) is a hereditary metabolic disorder charaterized by slowly progressive mental deterioration from infancy, urinary excretion o large amounts of aspartylglycosamine, and decreased activity of the lysosomal enzyme aspartylglycosamine amido hydrolase in various body tissues and fluids. The nature and distribution of the morphological and histochemical alterations in AGU are described in the light of the first AGU patient investigated post mortem and brain and liver biopsies from two additional patients. The most severe changes were noted in the brain and liver. Most nerve cells and hepatocytes contained large vacuoles without any histochemically demonstrable lipid or carbohydrate material. Ultrastructural studies revealed numerous electron-lucent vacuoles, limited by a single membrane, in the cytoplasm of these cells. In addition to evenly dispersed finely granular or reticular material the vacuoles contained small electron-opaque “lipid” droplets and polymorphic membraneous or granular aggregates. Similar vacuoles were also seen in a number of other cell types, particularly in the Kupffer cells and brain macrophages, as well as in the capillary pericytes. Biochemical studies suggest that the principal storage material consists of aspartylglycosamine itself; glycoasparagines of higher molecular weight are present as only minor components. Correlated morphological and biochemical studies thus definitely establish that AGU is a generalized storage disorder. The condition is apparently due to decreased activity of aspartylglycosamine amido hydrolase, with accumulation of products of glycoprotein catabolism in cytoplasmic vacuoles in both epithelial and mesenchymal cells.