Sialidase deficiency

It should be noted that sialidase deficiency has been observed386 in the liver of SM/J mice tested with 4-methylumbelliferyl a-Neu5Ac. 

Bach, G., Zeigler, M., Shaap, T., and Kohn, G., 1979, Mucolipidosis Ganglioside sialidase deficiency, Biochem. Biophys. Res. Commun. 90 1341-1347. 

Yamada, T., Tsuji, S., and Miyatake, T., 1983, Lysosomal sialidase deficiency in sialidosis with partial P-galactosidase deficiency, Biochim. Biophys. Acta 755 106-111. 

There are other lysosomal disorders in addition to those shown in Figure 9.20 and Table 9.1. For instance, several types of fucosidoses exist, which affect such structures as glycoproteins and blood group substances. Sialidoses also exist. However, lysosomal fucosidase and sialidase (neuraminidase) deficiencies do not affect the degradation of gangliosides. 

Suppose a patient had a sialidase (N-acetylneuraminidase) deficiency. Which substance do you not expect to accumulate in the patient s cells ... 

Mouse models are available for Tay-Sachs disease (a-chain deficiency), Sandhoff disease (p-chain deficiency), and GM2-activator deficiency (T. Kolter, 1998). The mice have phenotypes that are only slightly different from human GM2 gangliosidoses. However, the severity and course of the disease differs, and this has been attributed to species differences in the sialidase activity of the mouse versus human. The mouse siali-dase accepts GM2 as a substrate (shown by the dashed arrow in Fig. 10) (K. Sango, 1995) and converts it to GA2, which cannot be further degraded since the responsible enzyme is also deficient. 

In a patient classified as mucolipidosis I, Ckmzetal (1977) and Spranger /. (1977) demonstrated a severe deficiency of an acid neuraminidase (sialidase N-acetyl neuraminic acid hydrolase, E.C. 3.2.1.18) in his cultured fibroblasts. The patient had a neurodegenerative disorder with myoclonus, skeletal changes like in Hurler disease, and cherry-red spots in the maculae of his eyes. In addition to the neuraminidase defect, the fibroblasts of the patient accumulated abnormal amounts of sialic acid-containing compounds. The patient excreted excessive quantities of sialyloligosaccharides in the urine (Michalski etal 1977). Fibroblasts from the parents of another such patient had activities of neuraminidase which were intermediate between patients and controls (Cantz and... 

Not only the deficiency of a hydrolytic enzyme, but also of other proteins required for sphingolipid degradation can cause a sphingolipid storage disease. Besides deficiencies of activator proteins, this is the case in galactosialidosis. This disease is characterized by the secondary deficiency of P-galactosidase and sialidase activity. The primary defect is due to mutations within the protective protein, which forms a stable complex with the GMl-p-galactosidase and the lysosomal sialidase [47]. 

Deficient activity in lysosomal acid sialidase (a-neuraminidase) is the genetic defect underlying sialidosis. Sialic acid occurs at the nonreducing terminus of the carbohydrate chains of many glycoproteins and also as a characteristic component of gangliosides. However, there is no biochemical or enzymological... 

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