What is Familial Hypercholesterolemia?

Inheriting issues with cholesterol

Familial hypercholesterolemia (FH) is an inherited defect in how the body recycles LDL, or “bad” cholesterol.

People with FH are born with high LDL cholesterol. Everyone’s cholesterol levels tend to rise with age. But those with FH have LDL levels that start high and get higher over time.

High LDL contributes to plaque buildup, leading to a much higher-than-normal risk of coronary heart disease. If left untreated, people with FH have 20 times the risk of developing heart disease.

Causes of FH

Familial hypercholesterolemia is commonly caused by a mutation in the gene for the LDL cholesterol receptor, which is involved in passing LDL from the blood into cells for use by, or removal from, the body. Mutations in other genes also can cause inherited high cholesterol. Those genes include the PCSK9 gene and the gene for Apolipoprotein B. If you inherit a specific type of mutation in any of these three genes, you can develop FH.

How common is FH?

One in about 200 adults have the FH genetic mutation. Including children, FH affects about 1.3 million people in the U.S. But only about 10% are aware they have it. The good news: FH is treatable with medications and lifestyle changes.

Types of FH

There are two types of FH:

• Heterozygous FH (HeFH). This is the more common type and is inherited from one parent. In severe cases, LDL cholesterol levels can reach above 190 milligrams per deciliter (mg/dL) of blood. If left untreated, people with HeFH may develop heart disease as early as 30 years old.
• Homozygous FH (HoFH). This is a rare form and is inherited from both parents. LDL cholesterol levels can reach above 400 mg/dL of blood. If not detected and treated early, people with HoFH may develop heart disease in the first 10 years of life, sometimes as early as 2 or 3 years old. Learn more about HoFH.

Diagnosing FH

Both types of FH can be diagnosed with a physical exam and lab results, as well as personal and family history. They also can be discovered through molecular diagnosis, genetic diagnosis or genetic testing. It’s helpful when genetic testing reveals FH because it can alert relatives to their risk.

Some people with FH have physical symptoms. Many don’t.

One symptom is cholesterol deposits in the Achilles tendons or the tendons of the hands or elbows. People with HoFH also can develop cholesterol deposits in other areas, such as the skin surrounding the eyes or on the outer edge of the cornea.

If one person in a family has FH, then all immediate relatives — parents, siblings, children — should be checked for it. Similarly, if someone in a family has an early heart attack, it’s a good idea for other family members to get tested.

Children with increased risk for FH should be screened beginning at age 2. All children should have their cholesterol checked between ages 9 and 11 and again between ages 17 and 21.

What is cascade screening, and why is it important for identifying genetic conditions?

Cascade screening is a method used to identify individuals within a family who may be at risk of inheriting specific genetic conditions. It involves screening close relatives of a person diagnosed with a specific genetic condition to determine if they also have the same genetic mutation.

In the case of familial hypercholesterolemia and elevated Lp(a), early intervention can help manage LDL cholesterol levels and reduce the risk of cardiovascular disease.

Learn more about Cascade screening for FH (PDF).

Treating FH

FH remains underdiagnosed and undertreated. But people with FH have an excellent prognosis if the condition is identified early and treated. People with HoFH, or suspected HoFH, should start treatment as soon as possible. If not treated early, HoFH can lead to deadly cardiovascular complications in childhood.

Familial hypercholesterolemia cannot be treated by diet and exercise alone. These lifestyle changes can help, but medications are recommended to reduce LDL cholesterol levels by at least 50%.

Treatment usually involves a statin drug, and other cholesterol-lowering medications, such as ezetimibe, also may be required. People with extremely high LDL cholesterol, such as those with HoFH, may need a treatment called LDL apheresis. This is a dialysis-like procedure that’s done every few weeks to remove cholesterol from the blood.

Another class of lipid-lowering medications called bile acid sequestrants, which include cholestyramine or colesevelam, also may be used. These drugs reduce the amount of cholesterol absorbed by the intestines. This, in turn, lowers the amount of cholesterol that gets into the bloodstream.

Injectable medications, known as PCSK9 inhibitors, also can lower cholesterol levels. These medications target and block the PCSK9 protein, which frees up more receptors on liver cells to remove LDL cholesterol from the blood.

If you’ve been diagnosed with FH, talk to your health care professional about the right treatment plan for you. Also talk to your family members about FH so they can get screened and treated.