Familial defective apolipoprotein

Association between a specific apolipoprotein B mutation and familial defective apolipoprotein B-100. Proc Natl Acad Sci USA 1989 86 587-591. 

Marz W, Baumstark M, Scharnagl H, Ruzicka V, Buxbaum S, Herwig J, et al. Accumulation of small dense low density lipoproteins in a homozygous patient with familial defective apolipoprotein B-100 results from heterogenous interaction of LDL subfractions with the LDL receptor. J Clin Invest 1993 92 2922-2933. 

Myant NB. Familial defective apolipoprotein B-100 a review, including some comparisons with familial hypercholesterolaemia [published erratum appears in Atherosclerosis 1994 Feb 105[2] 253[. Atherosclerosis 1993 104 1-18. 

Schaefer JR, Scharnagl H, Baumstark MW, Schweer H, Zech LA, Seyberth H, et al. Homozygous familial defective apolipoprotein B-100. Enhanced removal of apolipoprotein E-containing VLDLs and decreased production of LDLs. Arter-ioscler Thromb Vase Biol 1997 17 348-353. 

H15. Hansen, P. S., Meinertz, H., Jensen, H. K., Fruergaard, P., Launbjerg, J., Klausen, 1. C., Lemming. L., Gerdes, U., Gregersen, N., and Faergeman-, O., Characteristics of 46 heterozygous carriers and 57 unaffected relatives in five Danish families with familial defective apolipoprotein Bin,. Atheroscler. Thromb. 14, 207-213 (1994). 

Lipoprotein(a) in subjects with familial defective apolipoprotein Bl00. Atherosclerosis (Shannon. Irel.) 92, 203-212 (1992). 

Miserez AR, Laager R, Chiodetti N, Keller U (1994) High prevalence of familial defective apolipoprotein B-100 in Switzerland. J Lipid Res 35 574-583... 

Tybjaerg-Hansen A, Gallagher J, Vincent J, Houlston R, Talmud P, Dunning AM, et al. Familial defective apolipoprotein B-lOO detection in the United Kingdom and Scandinavia, and clinical characteristics of ten cases. Atherosclerosis 1990 80 235-42. 

A specific mutation of apolipoprotein B results in defective binding of LDL to its receptor and produces an identical cl inical picture to FH called familial defective apo B (FDB). 

Tybiaerg-Hansen, A. and Humphries, S. (1992) Familial defective apolipoprotein B-100 a single mutation that causes hypercholesterolemia and premature coronary artery disease. Atherosclerosis, 96, 91. 

D. Reduced hepatic LDL-receptor activity. Familial hypercholesterolemia is most often due to dehcient LDL-receptor activity. A less likely possibility, although not considered in this question, is reduced LDL clearance from the circulation due to defective apolipoprotein Bioo. 

Fate of the remaining chylomicron components After most of tt triacylglycerol has been removed, the chylomicron remnan (which contain cholesteryl esters, phospholipids, apolipoprotein and some triacylglycerol) bind to receptors on the liver (seej 228) and are then endocytosed. The remnants are the hydrolyzed to their component parts. Cholesterol and the nitrogf nous bases of phopholipids (for example, choline) can be req cled by the body. [Note If removal of chylomicron remnants by th liver is defective, they accumulate in the plasma. This is seen i type III hyperlipoproteinemia (also called familial dysbetalipopro teinemia, see p. 229). 

Chylomicron remnants and very low density lipoprotein (VLDL) remnants are rapidly removed from the circulation by receptor-mediated endocytosis. ApoE, the major apolipoprotein of the chylomicron in the brain, binds to a specific receptor and is essential for the normal catabolism of triglyceride-rich lipoprotein constituents. Defects in apolipoprotein E result in familial dysbetalipoproteinemia, or type III hyperlipoproteinemia (HLP III), in which increased plasma cholesterol and triglycerides are the consequence of impaired clearance of chylomicron and VLDL remnants (Mahley et al., 1999). In the brain, lipidated apoE binds aggregated in a isoform-speciflc manner, apoE4 being much more effective than the other forms,... 

Remnant removal disease (RRD, also called remnant lipaemia, familial dysbetalipoproteinemia) (uncommon) in which there is a defect of apolipoprotein E. This is the major ligand that allows internalisation and subsequent metabolism of remnant particles derived from VLDL and chylomicrons. The consequence is accumulation of VLDL remnants called intermediate density lipoprotein (IDL) with cholesterol and triglycerides usually in the range 6-9 mmol/1. Patients experience severe macrovascular disease (as above). 

Results of these studies are providing additional evidence that distinct lipoprotein families or particles defined by their apolipoprotein composition represent the fundamental chemical and metabolic entities of the lipid transport system. The concept of lipoprotein families thus offers a new theoretical basis for describing, interpreting, and influencing processes responsible for normal as well as defective transport of triglycerides and other lipids. 

The classification of hyperUpidaemias is confusing as there are two means of classification - the Fredrickson based on the pattern of plasma lipoproteins in each condition, and the Goldstein based on the underlying enzyme defects. Type I hyperlipidaemia (Fredrickson) is a lipoprotein lipase or apolipoprotein-C2 deficiency. It leads to massive Hpid deposition and presents in childhood. Type Da hyperlipidaemia (familial hypercholesterolaemia) is a severe illness, not to be confused with common hypercholesterolaemia. Familial hypercholesterolaemia presents in childhood with deposits of cholesterol in the skin and ischaemic heart disease in adolescence. 

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