Familial Combined Hyperlipidemia and Familial Hypertriglyceridemia
Familial combined hyperlipidemia (FCHL) and familial hypertriglyceridemia (FHTG) are two common genetic forms of hyperlipidemia that differ in their clinical consequences and pathophysiology but are as yet poorly understood. The first is characterized by multiple lipoprotein phenotypes in affected relatives, an increase in plasma levels of apolipoprotein B (apo B), and a marked predisposition toward early-onset atherosclerosis. In FCHL, affected relatives can have increased plasma cholesterol and plasma triglyceride alone or in combination, with increased levels of LDL, very-low-density lipoprotein (VLDL), or both. Further, an affected individual might manifest any of these different plasma lipid and lipoprotein patterns at different stages of his/her life. In FHTG, affected individuals have primary elevations of their plasma triglyceride levels, with low-density lipoprotein (LDL) levels in the normal range. They do not appear to be particularly at increased risk for early-onset atherosclerosis. A major clinical consequence of this disorder, the chylomicronemia syndrome (Brunzell and Bierman, 1982), occurs when FHTG coexists with untreated diabetes or with the use of drugs that elevate plasma trigylceride levels (Chait and Brunzell, 1983), such as estrogens, alcohol, glucocorticoids, diuretics, and β blockers.
The precise pathogenetic mechanisms are not known for either disorder. This is in part because of lack of genetic markers, lack of appropriate animal models, and the inability thus far to detect homozygotes in whom metabolic defects are likely to be exaggerated. Studies of pathogenetic mechanisms in these disorders by and large rely on evaluation of plasma lipoproteins and their kinetics. A defect in hepatic production of lipoproteins appears to underlie both disorders. Difficulties in obtaining human liver for study have undoubtedly impeded progress in our understanding of these conditions.
KeywordsFamilial Hypercholesterolemia VLDL Particle Familial Combine Hyperlipidemia Major Clinical Consequence VLDL Triglyceride
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