Causes

Familial hypercholesterolemia is a genetic disorder caused by a defect on chromosome 19.

The defect makes the body unable to remove low density lipoprotein (LDL, or "bad") cholesterol from the blood. This results in high levels of LDL in the blood. High levels of LDL cholesterol make you more likely to have narrowing of the arteries from atherosclerosis at an early age. Those with familial hypercholesterolemia are more likely to have a family history of high cholesterol and heart disease at a younger age than normal.

The condition is typically passed down through families in an autosomal dominant manner. That means you only need to get the abnormal gene from one parent in order to inherit the disease.

In rare cases, a child may inherit the gene from both parents.When this occurs, the increase in cholesterol levels is much more severe, greatly increasing the risk for heart attacks and heart disease.

Symptoms

Symptoms that may occur include:

• Fatty skin deposits called xanthomas over the elbows, knees, buttocks, tendons, and around the cornea of the eye
• Cholesterol deposits in the eyelids (xanthelasmas)
• Chest pain (angina) or other signs of coronary artery disease; may be present at a young age

Exams and Tests

A physical examination may reveal fatty skin growths called xanthomas and cholesterol deposits in the eye (corneal arcus).

The doctor will ask questions about your personal and family medical history. There may be:

• A strong family history of familial hypercholesterolemia or early heart attacks
• High levels of LDL in either or both parents

Individuals from families with a strong history of early heart attacks should have blood tests done to determine lipid levels.

Blood tests may show:

• High levels of total cholesterol
  • Greater than 300 mg/dL in adults
  • Greater than 250 mg/dL in children
• High LDL levels
  • Greater than 170-200 mg/dL in children
  • Greater than 220 mg/dL in adults
• Normal level triglycerides

Other tests that may be done include:

• Studies of cells called fibroblasts to see how the body absorbs LDL cholesterol
• Genetic test for the defect associated with this condition

Treatment

The goal of treatment is to reduce the risk of atherosclerotic heart disease. Those who inherit only one copy of the defective gene may respond well to diet changes combined with statin drugs.

LIFESTYLE CHANGES

The first step is to change what you eat. This is tried for several months before drug therapy is added. Diet changes include reducing total fat intake to less than 30% of the total calories you eat.

You can reduce your saturated fat intake by:

• Decreasing amounts of beef, chicken, pork, and lamb
• Substituting low-fat dairy products for full-fat ones
• Eliminating coconut and palm oils

You can reduce your the amount of cholesterol you eat by eliminating egg yolks and organ meats.

Dietary counseling is often recommended to help people make these adjustments to their eating habits. Weight loss and regular exercise may also aid in lowering cholesterol levels.

See also: Heart disease and diet

MEDICATIONS

If lifestyle changes do not change your cholesterol levels, your doctor may recommend medication. There are several types of drugs available to help lower blood cholesterol levels, and they work in different ways. Some are better at lowering LDL cholesterol, some are good at lowering triglycerides, while others help raise HDL cholesterol.

The most commonly used and effective drugs for treating high LDL cholesterol are called statins. The include lovastatin (Mevacor), pravastatin (Pravachol), simvastatin (Zocor), fluvastatin (Lescol), atorvastatin (Lipitor), and rosuvastatin (Crestor).

Other cholesterol-lowering medicines include:

• Bile acid-sequestering resins
• Ezetimibe
• Fibrates (such as gemfibrozil)
• Nicotinic acid

Those with more severe forms of this disorder may need a treatment called extracorporeal apheresis. This is the most effective treatment. Blood or plasma is removed from the body. Special filters then remove the extra LDL-cholesterol, and the blood plasma is then returned.

Outlook (Prognosis)

How well you do greatly depends on whether or not you follow your doctor's treatment recommendations. Diet changes, exercise, and medications can lower cholesterol levels for those with the milder form of this disorder, and may significantly delay a heart attack.

Men and women with familial hypercholesterolemia typically are at increased risk of early heart attacks.

Risk of death varies among patients with familial hypercholesterolemia. Persons who inherit two copies of the defective gene have a poorer outcome. That type of familial hypercholesterolemia causes early heart attacks and is resistant to treatment.

Possible Complications

• Heart attack at an early age
• Heart disease

When to Contact a Medical Professional

Seek immediate medical care if you have chest pain or other warning signs of heart attacks.

Call for an appointment with your health care provider if you have a personal or family history of high cholesterol levels.

Prevention

A diet low in cholesterol and saturated fat and rich in unsaturated fat diet may help to control LDL levels.

Counseling is an option for those who have a family history of this condition, particularly if both parents carry the defective gene.

Alternative Names

Type II hyperlipoproteinemia; Hypercholesterolemic xanthomatosis; Low density lipoprotein receptor mutation

References

Genest J, Libby P. Lipoprotein disorders and cardiovascular disease In: Libby P, Bonow RO, Mann DL, Zipes DP, eds. Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine. 8th ed. Philadelphia, Pa: Saunders Elsevier; 2007:chap 42.

Mahley RW, Weisgraber KH, Bersot TP. Disorders of lipid metabolism. In: Kronenberg HM, Melmed S, Polonsky KS, Larsen PR, eds. Williams Textbook of Endocrinology. 11th ed. Philadelphia, Pa: Saunders Elsevier; 2008:chap 36.

Semenkovich CF. Disorders of lipid metabolism. In: Goldman L, Ausiello D, eds. Cecil Medicine. 23rd ed. Philadelphia, Pa: Saunders Elsevier; 2007:chap 217.

Update Date: 5/23/2012

Reviewed by: David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc., and David C. Dugdale, III, MD, Professor of Medicine, Division of General Medicine, Department of Medicine, University of Washington School of Medicine.