Cholesteryl ester storage disease

Wolman disease (cholesteryl ester storage disease)... 

Kale, A.S., Ferry, G.D., Hawkins, E.R End-stage renal disease in a patient with cholesteryl ester storage disease following successful hver transplantation and cyclosporine immunosuppression. J. Pediatr. Gastroenterol. Nutrit. 1995 20 95-97... 

Limbach, A., Steppberger, K., Nanmann, A., Sandig, K., Lohse, R, Keller, E. Cholesteryl ester storage disease as cause of hepatomegaly in childhood. Mschr. Kinderheilk. 2003 151 953—956... 

Once lipoprotein cholesterol enters the cell, the cholesteryl esters are hydrolyzed by lysosomal acid lipase. The lack or malfunction of this enzyme results in intracellular accumulation of cholesterol esters and produces a clinical disorder known as cholesteryl ester storage disease. 

M. J. Poznansky, K. J. Hutchison, and P. J. Davis. Enzyme replacement in fibroblasts from a patient with cholesteryl ester storage disease. FASEB J. 3 1525 (1989). 

Cholesteryl ester storage disease is a less severe form of Wolman syndrome in which a residual amount (1-5%) of lysosomal acid lipase activity is expressed [108,109]. Patients with this disease may survive until young adulthood. 

The anatomic sites (subcellularly) and the details of the enzymatic processes involved in the hydrolysis of chylomicron cholesteryl esters newly taken up by the liver have not been fully defined. It is clear that one of the major processes consists of receptor-mediated endocytosis of chylomicron remnants, followed by hydrolysis of cholesteryl esters and other remnant components within lysosomes. In rare genetic diseases characterized by lysosomal acid lipase deficiency (Wol-man s disease and cholesteryl ester storage disease), cholesteryl esters accumulate in liver cells and in other tissues as well [see Assmann and Frederickson (1983) for review and references]. An acid cholesteryl ester hydrolase from rat liver lysosomes has been partially purified and characterized (Brown and Sgoutas, 1980 Van Berkel etal., 1980). Enzymatic activity was found in preparations of both parenchymal and nonparenchymal liver cells (Van Berkel et al., 1980). Hydrolysis of chylomicron cholesteryl esters taken up by isolated rat hepatocytes was inhibited by chloroquine (Florin and Nilsson, 1977), an agent which inhibits the action of acid hydrolases in lysosomes. Finally, there is also evidence that the rate of cholesteryl ester hydrolysis may be limited by the rate at which internalized remnant particles are moved to the presumably lysosomal site of hydrolysis (Nilsson, 1977 Florin and Nilsson, 1977 Cooper and Yu, 1978). 

Further reading Fredrickson, D.S. and Ferrans, V.J. (1978). Acid cholesteryl ester hydrolase deficiency. (Wolman s disease and cholesteryl ester storage disease). In Stanbury, J.B., Wyngaarden, J.B. and Fredrickson, D.S. (eds.) The Metabolic Basis of Inherited Disease. 4th Edn., p. 670. (New York McGraw-Hill)... 

Apart from the hyperlipoproteinaemias that act as determinants of abnormal plasma lipoprotein concentrations, conditions with abnormally low concentrations of certain lipoproteins are also encountered and are generally referred to as the hypolipoproteinaemias. Tangier disease is one such condition that occurs as a rare inherited condition with autosomal recessive characteristics. The condition, a familial HDL deficiency, is characterized by cholesteryl ester accumulation in the reticuloendothelial system, which is similar in pattern to other lipid-storage diseases, such as gangliosidoses. Atheroma are substantially absent from the aorta and coronary vessels of such patients. The plasma cholesterol concentration is reduced and the triacylglycerol concentration is normal or increased in these cases. 

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