Gaucher Cerebrosides

One example is an enzyme replacement drug used to treat a form of Gaucher disease, which is caused by an inherited error in the gene coding for the enzyme that breaks down the fatty substance cerebroside. In Gaucher disease, certain immune system cells... 

Cerebroside—Fatty substance that fills up blood cells in Gaucher disease. 

Tay-Sachs Gaucher s Niemann-Pick Brain Spleen, Uver Several, particularly liver and spleen Glycolipid (gangUoside G t) Cerebrosides containmg glucose Sphingomyelins... 

Tay-Sachs, Gaucher s, and Niemann-Pick 8.38 Cerebrosides, brain tissue... 

Several diseases—Gaucher s, Tay-Sachs, Niemann-Pick, and Fabry s diseases, and the leukodystrophies— are characterized by accumulation of lipoid material in cells. These diseases differ in the composition and site of the lipoid accumulation. Whereas gangliosides accumulate in Tay-Sachs disease, sphingosides are found in Niemann-Pick disease, and cerebrosides in... 

Gaucher s disease. Gangliosides accumulate primarely in the cells of the nervous system, but sphingosides and cerebrosides pile up in the reticuloendothelial cells [108, 109]. 

Gaucher s disease is a hereditary disease transmitted by an autosomal recessive or dominant gene and characterized by the accumulation of cerebrosides in reticuloendothelial cells. 

Clinical Pathology. When Gaucher described the disease for the first time, he emphasized three symptoms splenomegaly, hepatomegaly, and skin pigmentation. Later, lipoid material was found in the reticuloendothelial cells, and 1924 it was shown that the compounds that accumulate in those cells are cerebrosides [116-119]. 

Cerebroside Structure and Metabolism. The structure of cerebrosides is particularly important because it has been claimed that those that accumulate in Gaucher s disease are abnormal. The general formula of cerebrosides includes equimolecular amounts of hexose, sphingosine, and fatty acids. 

It is important to know when in the course of brain development cerebrosides are synthesized because such information might give some clues on the pathogenesis of Gaucher s disease and also some forms of mental deficiency. In rodents, cerebrosides are not actively synthesized during embryonic life or at birth. In mice, the incorporation of labeled hexoses in cerebrosides occurs approximately four days after birth and in rats, seven days after birth. In either case, the synthesis of brain cerebrosides seems to precede that... 

Cerebrosides accumulate in the reticuloendothelial cells in Gaucher s disease. The cerebroside content of spleen and liver is increased tenfold however, an increase in the cerebroside content of brain has not been convincingly demonstrated. 

Fredrickson, D.S. Cerebroside lipidosis Gaucher s disease. In The metabolic basis of inherited disease (Stanbury, J.B., Wyngaarden, J.B., and Fredrickson, D.S., eds.), 2nd ed., p. 565-585. New York McGraw-Hill Book Company 1966... 

Normal cerebrosides from brain are galactocerebrosides. An accumulation of glucocerebrosides has been found in Morbus Gaucher (Klenk 1940 Rennkamp 1942). 

Agranoff, B. W., N. Rad in, and W. Suomi Enzymic oxidation of cerebrosides studies on Gaucher s disease. Biochim. biophys. Acta (Amst.) 67,194 (1962). 

The cerebroside content of the brain is very low and comparable to that of the infantile brain (Rouser et al. 1965). There is no increase with progression of the disease. Since cerebrosides and sphingomyelin are the main components of the myelin-lipids, a decrease of these classes is in accordance with the histologic finding of demyelination (Brante 1949, Johnson et al. 1949). Similar changes occur in Niemann-Pick disease with central nervous system involvement, in meta-chromatic leucodystrophy and in Alzheimer s disease (Rouser et al. 1965). The case of WiLDi (1950) which has been reported as a mixed type of TSD and Gaucher s disease is an exception since here cerebrosides were increased in addition to gangliosides. 

Fig. 5. GD. Bono marrow. HE-stain. Enlargement 900-fold. Reticulum cells are transformed to Gaucher cells and store cerebrosides which impart to the cytoplasm a crumbled tissue paper appearance. (Reproduced by courtesy of Prof. P. B. Diezel)...

The increased cerebroside content of many tissues has stimulated numerous attempts to measure plasma cerebroside levels, but a lack of appropriate methods has hampered such studies until recently. Thus, Jones and Thannhauser did not find differences between Gaucher patients and normals with values of 1.23 and 1.83 mg per 100 ml respectively in two subjects with GD and 1.83 mg per 100 ml in the serum of a healthy person. 

In 1958 SvENNERHOLM determined the normal serum cerebroside level with newer methods and found a value of 4.36 0.18 mg per 100 ml. The average serum cerebroside level in 6 splenectomized Gaucher patients was twice normal, namely... 

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