Cholesterol ester storage disease

One limitation of enzyme replacement therapy is the targeting of enzyme proteins to appropriate sites of substrate accumulation. Administration of a cholesterol esterase conjugated to albumin results in the degradation of pathologic cholesterol ester accumulations within the lysosomes of fibroblasts from a patient with cholesterol ester storage disease (246). 

Wolman s disease Cholesterol ester storage disease Acid lipase Cholesterol ester... 

Cholesterol esters Wolman disease, CESD (cholesterol ester storage disease) Acid lipase 10q23.2-q23.3... 

Fig. 21.5 Cholesterol ester storage disease (CESD). Micro-/macro-vesicular fat droplets in hepatocytes and foam cells in a portal tract (Sudan III)...

Fig. 31.13 Cholesterol ester storage disease. Fine-droplet fatty changes in the hepatocytes. Widely extensive small and larger lipid vacuoles in the liver cells and foam cells of the portal field (Sudan black) (s. fig. 21.5). Same patient as in fig. 31.14...

Beaudet, A.L., Ferry, G.D., Nichols, B.F.jr., Rosenberg, H.S. Cholesterol ester storage disease clinical, biochemical, and pathological studies. J. Pediatr. 1977 90 910-914... 

Other rare lipid-storage diseases include Wolman s disease (triacylglycerol and cholesterol accumulation), hepatic cholesterol ester storage disease, ceroid storage disease, histiocytosis X, lipid proteinosis, lipid dermatoarthritis and Farber s disease (see Table 12.5 involves storage of acid mucopoly-... 

Acid lipase (EC 3.1.3.2). Cholesterol esters and triacylglycerols deposited in adrenals, liver, spleen, bone marrow, capillaries, endothelium, ganglion cells of mesenteric plexus and mucosa of small intestine. Plasma lipids mainly normal. Hepatosplenomegaly. Adrenal calcification and enlargement. Failure to thrive in infancy, rapid deterioration and death. Auto-somai recessive. See Cholesterol ester storage disease. 

Cholesterol ester storage Niemann-Pick disease... 

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. 

Lymphadenopathy is most often not clinically manifested however, bright yellow plaques and a cholesterol ester content 100-fold higher than normal have been documented for both normal-size and enlarged lymph nodes in Tangier patients. Biopsies of bone marrow and the affected tissues have revealed many foam cells that are smaller than those observed in lipid storage diseases. In addition, these cells contain sudanophilic deposits which are not membrane-bound, as is the case for lysosomal storage diseases. Foam cells have also been found in otherwise normal skin, ureters, renal pelvises, tunica albuginea (white fibrous capsule) of testicles, mitral and tricuspid valves, and aorta, coronary, and pulmonary arteries. 

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. 

Tangier disease (TD) is a very rare disorder which is named after the island of Tangier in the Chesapeake Bay where the first cases have been found. It is characterized by very low concentrations in plasma of high density lipoproteins (HDL) and by storage of cholesterol esters in various organs, particularly in those belonging to the reticuloendothelial system. 

The disease has been named after the isle of Tangier off the coast of Virginia where the first cases have been observed. It is characterized by the almost complete absence of high-density lipoproteins and storage of cholesterol and its esters in various tissues. The first observation concerned a five year old boy and his six year old sister. They had no further siblings. Further inquiries revealed that the parents were distantly related. Meanwhile two more affected families have been found in Missouri and Kentucky. The affected families are unrelated (Fredrickson et al. 1962, 1964). 

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