Laboratory Diagnosis and Classification of Dyslipoproteinemias

Frederikson’s classification of dyslipoproteinemias is based on clinical features and electrophoretic or ultracentrifugal pattern of lipoprotein fractions. It was recognized as the international standard of dyslipoproteinemia classification in 1972 by the World Health Organization. Type I dyslipoproteinemia is represented by three rare genetic disorders, i.e., familial lipoprotein lipase deficiency, familial apolipoprotein C-II deficiency and lipoprotein lipase deficiency due to familial inhibitor of lipoprotein lipase, which are inherited in autosomal recessive pattern. It is characterized by hyperchylomicronemia due to decreased activity of lipoprotein lipase, increasing the risk of pancreatitis and cardiovascular diseases. Type II dyslipoproteinemia is represented by two disorders i.e., familial hypercholesterolemia and polygenic hypercholesterolemia. Familial hypercholesterolemia is autosomal dominant disease, caused by mutations in several genes (LDLR, APOC2, PCSK9 and LDLRAP1). It is characterized by an elevation of LDL cholesterol concentration in blood due to dysfunctional or absent LDL receptors, which results in skin changes and highly increased risk of cardiovascular diseases. Familial combined hyperlipidemia is IIb dyslipoproteinemia, which is characterized by increased VLDL and LDL synthesis due to hypersecretion of apolipoprotein B, hypercholesterolemia and hypertriglyceridemia and increased risk of cardiovascular diseases. Dysbetalipoproteinemia is type III dyslipoproteinemia, caused by apoE2/E2 genotype inherited in an autosomal recessive pattern, which results in compromised migration of intermediate density lipoprotein and chylomicron remnants to the liver. It is characterized by hypercholesterolemia and hypertriglyceridemia, skin changes and increased risk of cardiovascular disease. Type IV dyslipoproteinemia is represented by a polygenic multifactorial disease - familial hypertriglyceridemia, which is characterized by increased synthesis and compromised excretion of VLDL’s, which results in hypertriglyceridemia and increased cardiovascular disease risk. Type V dyslipoproteinemia is represented by a polygenic multifactorial disease - hyperprebetalipoproteinemia, which is characterized by increased VLDL synthesis, reduced lipoproteinlipase activity and results in hypertriglyceridemia, skin changes, increased risk of pancreatitis and cardiovascular diseases. Decreased HDL is the most common lipoprotein abnormality in patients with cardiovascular diseases. Dyslipoproteinemias can be caused by secondary, non - genetic factors, their clinical features and prognosis are similar to the genetic ones.