Disorders of Lipoprotein Metabolism

Summary

Disorders of lipoprotein metabolism-dyslipoproteinemias-can be classified based on the primary biochemical disturbance, such as high or low plasma levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, or triglyceride (TG), or some combination of these. Lipoproteins are physiological transporters of hydrophobic lipids and fat-soluble vitamins through plasma from their site of origin (intestine or liver) to their site of uptake and disposition. Abnormal levels of certain plasma lipids and lipoproteins increase the risk of cardiovascular disease (CVD) end points, such as myocardial infarction and stroke, and other complications such as pancreatitis. Numerous genetic and environmental factors contribute to inter-individual variation in plasma concentrations of lipids and lipoproteins. Disorders with a monogenic basis typically present earlier in life, while those that present later in life also have genetic, mainly polygenic, determinants, but their expression further depends on interactions with nongenetic environmental or lifestyle factors. Early diagnosis is central to specific dietary, lifestyle, and pharmacological interventions to delay death, disability, and medical complications. For example, to prevent premature CVD in heterozygous familial hypercholesterolemia, it is important to screen subjects at risk, make the appropriate diagnosis (which may include DNA analysis), and initiate treatment, which includes diet, exercise, and lipid-lowering medications. Here we describe the current understanding of genetic determinants, clinical manifestations, and treatment of disorders of lipoprotein metabolism, focusing on defined monogenic disorders that are diagnosed throughout the lifespan.