Familial hypercholesterolemia

Definition

Familial hypercholesterolemia is a condition passed down through families in which a person has high levels of "bad" cholesterol (low density lipoprotein, or LDL) beginning at birth. The condition can cause heart attacks at an early age.

See also:

• Familial combined hyperlipidemia
• Familial hypertriglyceridemia
• Familial dysbetalipoproteinemia

Alternative Names

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

Causes, incidence, and risk factors

Familial hypercholesterolemia is caused by a gene defect on chromosome 19. The defect makes the body unable to remove LDL cholesterol from the bloodstream. This results in consistently high levels of LDL in the blood, which leads to atherosclerosis at an early age.

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. An individual who inherits one copy of the gene is considered "heterozygous."

In rare cases, a child may inherit the gene from both parents. Individuals who inherit both genes are considered "homozygous." Homozygous familial hypercholesterolemia is much more severe. Cholesterol levels may exceed 600mg/dL, greatly increasing the risk for heart attacks and heart disease.

Symptoms

Symptoms that may occur include:

• Fatty, cholesterol-rich skin deposits (xanthomas)
• Cholesterol deposits in the eyelids (xanthelasmas)
• Chest pain (angina) associated with coronary artery disease
• Obesity

Persons with either one or two copies of the defective gene can develop fatty skin deposits over their elbows, knees, buttocks, tendons, and around the cornea of the eye.

Signs and tests

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

Other signs include:

• 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
• LDL greater than 200 mg/dL
• High level of triglycerides

Other tests that may be done include:

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

Treatment

Proper diet, exercise, and certain medications can bring lipids (fats in the blood) down to safer levels and reduce your risk of heart disease and heart attacks. Those who inherit only one copy of the defective gene may respond well to diet changes combined with statin drugs.

The first step is to change what you eat. You typically follow a modified diet for several months before your doctor adds on medications. You'll be told to decrease fat intake to less than 30% of the total calories you get each day.

You can reduce fat intake by:

• Eating less beef, pork, and lamb
• Choosing low-fat dairy products
• Avoiding coconut and palm oil

Cholesterol intake is reduced by avoiding:

• Egg yolks
• Organ meats
• Sources of animal-derived saturated fat

Further reductions in the percentage of fat in the diet may be recommended. For more information, see: Heart disease and diet.

Exercise, especially to induce weight loss, may also aid in lowering cholesterol levels.

Drug therapy may be started if diet, exercise, and weight-loss efforts have not lowered your cholesterol levels over time. Several cholesterol-lowering drugs are available, including:

• Bile acid sequestrant resins (cholestyramine and colestipol)
• Fenofibrate
• Gemfibrozil
• Nicotinic acid (niacin)
• Statin drugs

In rare cases, persons who inherited two copies of the defective gene may need surgery such as a liver transplant.

Expectations (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, 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.

Complications

• Heart attack at an early age
• Heart disease

Calling your health care provider

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

Call for an appointment with your health care provider if you have a 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.

References

Gaziano M, Manson JE, Ridker PM. Primary and secondary prevention of coronary heart 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 45.