Metabolic abnormalities in hyperlipidemias

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The role of hyperlipidemias as risk factors for coronary heart disease is widely acknowledged. After the first classification by Fredrickson based on plama lipid concentrations, a more comprehensive evaluation of the genetic background and the biochemical mechanism underlying these diseases is internatinally adopted nowadays. In familial hyperchylomicronemia, a tipically pediatric disease transmitted as autosomical recessive trait, postprandial chylomicrons accumulate in fasting plasma due to lack or impaired activation of lipolytic enzyme lipoprotein lipase (LPL). In polygenic hypercholesterolemia a moderate increase of low density lipoprotein (LDL) cholesterol is due to a combination of environmental and genetically transmitted factors, like, for instance, some isoforms of apolipoprotein (apo) E. In familial hypercholesterolemia, transmitted as autosomical dominant trait, the basic defect is the lack or defective activity of LDL receptors, particularly in the liver. This disease, particularly in its homozygous form, is a pediatric disease. In the broad beta disease (former type III) cholesterol enriched, small very low density lipoprotein (VLDL), also called intermediate density lipoprotein (IDL), build up in plasma. These patients show a reduced VLDL catabolism, due to a particular isoform af apo E, coupled with an increased VLDL production. An enhanced liver synthesis of Apo B is the abnormality underlying familial combined hyperlipidemia. Accumulation in plasma of VLDL, LDL or both depends on the coexistence of defects in their respective catabolism. Familial hypertriglyceridemia, characterized by massive accymulation of VLDL in plasma, is poorly understood, although an increased production of VLDL particles is usually detectable. Growing attention as risk factor for CVD is also being paid to elevated plasma concentrations of lipoprotein a Lp(a), a LDL-like particle whose structure resembles that of plasminogen and might therefore interfere with antithrombotic mechanism. The mechanisms underlying some secondary form of hyperlipidemias that are of pediatric interest are also examined. Hypertriglyceridemia is the common feature of obesity, insulin dependent diabetes mellitus and glycogen storage disease, while hypercholesterolemia is the most prevalent lipid abnormality in nephrotic syndrome.