Lecithin:cholesterol acyltransferase deficiency

F6. Forte, G. M., Norum, K. 11., Glomset, J. A., and Nichols, A. V., Plasma lipoproteins in familial lecithin cholesterol acyltransferase deficiency structure of low- and high-density lipoproteins as recorded by electron microscopy. J. Clin. Invest. 50, 1141-1148 (1971). 

Tl. Torsvik, H., Presence of ai-lipoprotein in patients with familial plasma lecithin cholesterol acyltransferase deficiency. Scand. J. Clin. Lab. Invest. 24, 187-196 (1969). 

Rare genetic disorders, including Tangier disease and LCAT (lecithin cholesterol acyltransferase) deficiency, are associated with extremely low levels of HDL. Familial hypoalphalipoproteinemia is a more common disorder with levels of HDL cholesterol usually below 35 mg/dL in men and 45 mg/dL in women. These patients tend to have premature atherosclerosis, and the low HDL may be the only identified risk factor. Management should include special attention to avoidance or treatment of other risk factors. Niacin increases HDL in many of these patients. Reductase inhibitors and fibric acid derivatives exert lesser effects. 

Funke H, Eckardstein A von, Pritchard PH, Karas M, Albers JJ, Assmann G (1991) A frame-shift mutation in the human apolipoprotein A-I gene causes high density lipoprotein deficiency, partial lecithin cholesterol-acyltransferase deficiency, and corneal opacities. J Clin Invest 87 371-376... 

ApoE is thought to reach the plasma from the liver in nascent HDL, diskshaped particles about 4.6-nm thick and with a mean diameter of about 19 nm which have clearly been shown to be of hepatic origin in the rat (H5). In plasma from human subjects with lecithin cholesterol acyltransferase deficiency a similar population of apoE-rich HDL particles, 14-40 nm in diameter and 4.4-4.5 nm thick, is seen (M37, S47). 

M37. Mitchell, C. D., King, W. C., Applegate, K. R., Forte, T., Clomset, J. A., Norum, K. R., and Cjone, E., Characterization ofapolipoprotein E-rich high density lipoproteins in familial lecithin cholesterol acyltransferase deficiency. /. Lipid Res. 21, 625-634 (1980). 

Soutar, A. K., Night, B. L., and Myant, N. B., The characterization oflipoproteins in the high density fraction obtained from patients with familial lecithin cholesterol acyltransferase deficiency and their interaction with cultured human fibroblasts. /. lipid Res. 23, 380-390 (1982). 

Familial lecithin Cholesterol acyltransferase deficiency, including fish eye disease, K. R. Norum, E. Gjone and J. 

A complete absence of LDL in the plasma is seen in patients with the rare autosomal recessive disorder, abetalipoproteinaemia. The patients may also have associated lecithin cholesterol acyltransferase deficiency which is also encountered as an independent conditon. In this latter case lipoproteins with abnormal flotation, size and compositional properties exist, with disc-shaped structures (nascent HDL particles ) being present at high concentration. 

The detection of abnormal lipoproteins can be done more effectively from the elution patterns monitored by protein or choline-containing phospholipids for the isolated lipoprotein fraction by the ultracentrifugation. In Fig. 20, the elution patterns of choline-containing phospholipids for each ultracentrifugal fraction are presented for three subjects normal female and patients with acute hepatitis and lecithin cholesterol acyltransferase deficiency. In contrast to normal subjects, all lipoprotein fractions for two pathological cases show the existence of abnormal lipoproteins in which a correlation between the particle size and density dose not exist. 

Furbee JW Jr, Sawyer JK, Parks JS. Lecithin.cholesterol acyltransferase deficiency increases atherosclerosis in the low density lipoprotein receptor and apolipoprotein E knockout mice. J Biol Chem 2002 277 3511-3519. 

Ng DS, Maguire GF, Wylie J, et al. Oxidative stress is markedly elevated in lecithin cholesterol acyltransferase-deficient mice and is paradoxically reversed in the apolipoprotein E knockout background in association with a reduction in atherosclerosis. 7 Bio/ Chem 2002 277 11,715-11,720. 

Kuivenhoven, J., Pritchard, H., Hill, J-, Frohlich, J., Assman, G.,and Kastelein, J. (1997). The molecular pathology of lecithin Cholesterol acyltransferase (LCAT) deficiency syndromes. J. Lipid Res. 38,191-205. 

Carlson LA, Holmquist L (1985) Evidence for deficiency of high-density lipoprotein lecithin-cholesterol acyltransferase activity (a-LCAT) in Fish Eye disease. Acta Med Scand 218 189-196... 

LCAT deficiency (complete) Lecithin cholesterol acyltransferase (LCAT) Liver 16q22 245900... 

Fig. 28.1. A schematic diagram depicting lipoprotein metabolism and the known genetic defects affecting lipoproteins. 28.1, Lipoprotein lipase (LPL) deficiency 28.2, apoC-II deficiency 28.3, apoE deficiency or mutations 28.4, hepatic lipase (HL) deficiency 28.5, LDL receptor deficiency or mutations 28.6, apoB-100 mutation in receptor binding region 28.7, apoA-I deficiency or mutations 28.7.3, ABCAl deficiency or mutations 28.8, LCAT deficiency 28.9, microsomal transfer protein (MTP) deficiency 28.10, apoB-100 synthesis or truncation mutations. Abbreviations C-II, apoC-II B, apoB E, apoE A-I, apoA-I VLDL, very-low-density lipoproteins IDL, intermediate-density lipoproteins LDL, low-density lipoproteins HDL, high-density lipoproteins LPL, lipoprotein lipase HL, hepatic lipase LCAT, lecithin cholesterol acyltransferase UC, unesterified cholesterol...

According to the above developed scheme of HDL and LDL structure, the molecular structure of cholesteryl esters is an important determinant to the size and internal arrangement of lipoproteins. This is further demonstrated by the structures of lipoprotein particles which lack cholesteryl esters. A natural system, where this is the case, is given by the abnormal lipoprotein Lp-X oc-curing abundantly in the serum of patients suffering from obstructive jaundice or from a familial deficiency in the enzyme lecithin-cholesterol-acyltransferase, which controls the conversion of cho-... 

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