Neuraminidase Studies in Sialidosis

Abstract

In 1968, two patients were described in the literature who exhibited clinical features resembling Hurler disease, yet had a normal urinary excretion of acid mucopolysaccharides. Histological and ultrastructural studies of neuronal, visceral and mesenchymal tissues revealed the lysosomal storage of compounds thought to be acid mucopolysaccharides and glycolipids (BÉRARD et al., 1968; SPRANGER et al., 1968; FREITAG et al., 1971) Together with morphologically similar disorders, these patients were later classified as mucolipidosis I (SPRANGER and WIEDEMANN, 1970). More recent biochemical investigations showed an accumulation of sialic acid-containing compounds in cultured fibroblasts and in leukocytes of such patients (CANTZ et al., 1977; SPRANGER et al., 1977; KELLY and GRAETZ, 1977), and a massive urinary excretion of sialyl oligosaccharides, whose structures resembled the glycan portion of glycoproteins MICHALSKI et al., 1977). In fibroblasts, there was a profound deficiency of an “acid” (presumably lysosomal) neuraminidase towards substrates such as sialyllactose, fetuin, and methoxyphenyl neuraminic acid, whereas other lysosomal hydrolases were within the normal range (CANTZ et al., 1977; SPRANGER et al., 1977; KELLY and GRAETZ, 1977). From these studies it became evident that the metabolic defect in mucolipidosis I consists of an impaired catabolism of glycoproteinderived sialyl oligosaccharides due to the genetic deficiency of a neuraminidase, i.e., that the disease is a sialidosis.