Sphingolipids sphingolipid storage diseases

Broad screening test for sphingolipid-storage diseases. Lancet 1999 354 901-905. 169. 

Puri V, Watanabe R, Dominguez M, et al. (1999) Cholesterol modulates membrane traffic along the endocytic pathway in sphingolipid-storage diseases. Nat Cell Biol 1 386-388... 

Breakdown of GSL occurs in the lysosomes, and inherited deficiencies of lysosomal hydrolases or of sphin-golipid activator proteins (SAPs, saposins) can give rise to sphingolipid storage diseases. The SAPs are necessary... 

Pagano RE, Puri V, Dominguez M, Marks DL. Membrane traffic in sphingolipid storage diseases. Traffic 1(2000) 807-815. 

Marks, D.L., Pagano, R.E. 2002. Endocytosis and sorting of glycosphingolipids in sphingolipid storage disease. Trends Cell Biol. 12 605-613. 

There are a number of recent reviews of the sphingolipidoses such as those of van Bogaebt et al., 1957 Volk and Spebby, 1959 Stanbuby et al., 1960 Folch-Pi, 1961 Abonson and Volk, 1962 and Folch-Pi and Baueb, 1963. The following selectively document the known sphingolipid storage diseases with newer references and mention briefiy several recent observations. 

The adult form of Gaucher disease (type I) is currently the only sphingolipid storage disease for which a causal therapy is available [33]. The patients are treated with a modified glucocerebrosidase from human placenta or a recombinant sample. The protein carbohydrates contain the targeting information for the mannose receptor on macrophages. 

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]. 

Figure 9.20 Degradation of sphingolipids. Lipid storage diseases are indicated by brackets as follows TS, Tay-Sachs ML, metachromatic leukodystrophy GG, generalized gangliosidosis G, Gaucher s disease NP, Niemann-Pick disease K, Krabbe s disease F, Fabry s disease. The sulfate residue on galactocerebroside is located on position 3 of the galactose residue. Note the sequential nature of the process if one step cannot take place, all subsequent steps cannot take place, either.

Table II. Genetic Lipid Storage Diseases Involving Sphingolipid Hydrolysis ...

Lipid storage diseases Deficiencies of Sphingolipid storage... 

Each lysosomal storage disease (see p. 49) is caused by a hereditary deficiency of an enzyme required for the degradation of a specific metabolite. Several lysosomal storage diseases are associated with sphingolipid metabolism. Most of... 

Inui, K., and Wenger, D. A., Concentrations of sphingolipid hydrolases in liver and brain samples from patients with lysosomal storage diseases. J. Clin. Invest. 72, 1622-1628. (1983). 

Sphingolipids are degraded by lysosomal enzymes (see Chapter 30). Deficiencies of these enzymes result in a group of lysosomal storage diseases known as the sphingolipidoses. 

Sphingolipidoses Lysosomal storage diseases (see) resulting from defective catabolism of glycoso-sphingolipids. 

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