Primary Genetic Dyslipidemias
There are five primary, genetically-inherited dyslipidemias.
Dyslipidemia Lab Values
Familial hypercholesterolemia Very high levels of cholesterol
Familial combined hyperlipidemia High levels of cholesterol and triglyceride
Familial dysbetalipoproteinemia High levels of cholesterol and triglyceride
Polygenic hypercholesterolemia High levels of cholesterol
Familial hypertriglyceridemia Very high levels of triglyceride
Familial Hypercholesterolemia
Familial hypercholesterolemia is a problem with either a completely defective or absent LDL receptor. There are two separate genetic types. Homozygous hypercholesterolemia results in cholesterol levels from 800 to 1200 mg/dl. These patients die usually from coronary artery disease by the age of 20. Heterozygous have much lower levels of cholesterol, usually under 300 mg/dl and die from coronary artery disease by age 50. Triglycerides will usually be normal. Tendon xanthomas are characteristic of this condition.
Familial Combined Hyperlipidemia
Familial combined hyperlipidemia will result in both high levels of cholesterol and triglycerides. Patients are susceptible to premature coronary artery disease. This illness is due to excessive hepatic production of apoprotein B.
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Familial Dysbetalipoproteinemia
Familial dysbetalipoproteinemia will result in both high levels of cholesterol and triglycerides. It is caused by impaired apoprotein E, which results in abnormal clearance of VLDL by the liver. Xanthomas in the crease of their palms and soles of their feet are characteristic of this disorder. Familial dysbetalipoproteinemia has an abnormal apo protein E. Thus, it binds poorly to hepatic receptors and it impairs the circulating LDL remnants. Apo protein E is used to bind to the hepatic receptors. This will impair the clearance of circulating VLD. These patients will
often have xanthomas in the crease of their palms and soles of their feet. It is very characteristic of this disorder.
Polygenetic Hypercholesterolemia
Polygenetic hypercholesterolemia is due to several inherited genetic defects in cholesterol metabolism. This is the most common cause for elevated fats. These people will have mild to moderate serum cholesterol elevation. This will often be found within the context of insulin resistance and truncal obesity in Syndrome X. Polygenetic hypercholesterolemia is due to several inherited genetic defects in cholesterol metabolism. These people will have mild to moderate serum cholesterol elevation. Polygenic means that it affects many genes. Often you will see these type of patients within that context of Syndrome X, with high lipids, high circulating insulin or insulin resistance, and truncal obesity.
Familiar Hypertriglyceridemia
Familiar hypertriglyceridemia is due to an excessive hepatic triglyceride synthesis. The difference between combined hyperlipidemia and familiar dysbetalipoproteinemia is both high cholesterol and high triglycerides, while familiar hyperlipidemia has an increase of apoprotein B receptors, and the dysbetalipoprotein has a normal Apo B but an abnormal Apo E. Familial hyperlipidemia will have elevated Apo B receptors.
Secondary Dyslipidemias
Secondary dyslipidemias are all secondary causes of serum lipid elevations from other illnesses.
Diabetes mellitus, hypothyroidism, nephrotic syndrome, renal disease, and obstructive liver disease can contribute to dyslipidemias.
Iatrogenic causes include beta blockers and diuretics, progestins, androgens, estrogens, retinoids (such as Accutane), analog of vitamin A, corticosteroids, anti-convulsant medications, Cyclosporin, and HIV drugs. Many of the drugs used in treating secondary complications of diabetes, such as beta blockers and diuretics, are helpful in treating the hypertension and edema, but cause other secondary complications of diabetes, such as dyslipidemia. Cardiovascular disease is the highest significant risk for a diabetic.
