What Is Heterozygous Familial Hypercholesterolemia?

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Familial hypercholesterolemia (FH), also called pure hypercholesterolemia, is an inherited condition in which a person's body is unable to effectively get rid of extra LDL cholesterol ("bad" cholesterol). This causes high levels of LDL in the blood, which can lead to a significantly increased risk of heart disease.

Heterozygous familial hypercholesterolemia (HeFH) is a type of FH in which a person inherits one faulty gene from one biological parent that is paired with a healthy gene from the other biological parent.

This article will review the symptoms, risk factors, and treatment for HeFH.

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Types of Familial Hypercholesterolemia

The types of FH refer to the way the genes that cause them are inherited.

FH is an autosomal dominant condition. This means that the gene that causes it is on one of the non-sex chromosomes (structures within cells containing genetic material) and it is dominant (takes control) over the healthy gene.

Because FH is autosomal dominant, all it takes is one FH gene (from one parent) to affect LDL levels, even if its paired gene (from the second parent) is healthy.

Whether one or both genes are affected determines the type of FH you have, and it influences how severe the condition manifests.

Heterozygous Familial Hypercholesterolemia (HeFH)

HeFH happens when one faulty gene is inherited from one parent and one healthy gene is inherited from the other parent.

This is the most common type of FH, affecting about one in 250 individuals.

Homozygous Familial Hypercholesterolemia (HoFH)

HoFH occurs when an individual inherits two faulty genes (one from each parent).

It is more serious than HeFH. Without aggressive treatment, severe vascular disease, including coronary artery disease (a buildup of plaque in the arteries that supply blood to the heart) and aortic stenosis (a narrowing of the aortic valve opening), often occur early in young adulthood, sometimes even in the teenage years.

HoFH is very rare, affecting about one in 250,000 individuals. Most people with FH have HeFH.

Symptoms of Heterozygous Familial Hypercholesterolemia

The main indication of HeFH is LDL cholesterol levels that are over 190 milligrams per deciliter (mg/dL) in adults or over 160 mg/dL in children.

HeFH increases the risk of heart disease, particularly atherosclerosis (hardening and/or narrowing of the arteries due to a buildup of fats, cholesterol, and other substances, called plaque).

The risk of heart disease starts early with HeFH, but symptoms may not be apparent, especially in the early stages.

Some symptoms of HeFH include:

  • Clusters of fatty skin growths around the body, usually the hands, knuckles, elbows, knees, ankles, and around the cornea of the eye (children with these nodules should be screened for FH)
  • Cholesterol deposits (yellowish globs) in the eyelids
  • Yellowish areas around the eyes
  • Arcus cornealis: A whitish-gray ring on the outside of the cornea
  • Cramping of one or both calves, especially when walking
  • Swollen or painful Achilles tendon (area along the back of the ankle and heel)
  • Angina (tightness or pressure in the chest)
  • Shortness of breath
  • Sudden stroke-like symptoms: Such as trouble speaking, drooping on one side of the face, weakness of an arm or leg, and/or loss of balance

Causes

HeFH is caused by a defect on chromosome 19. This defective gene is passed on to a child from one parent, while the child receives a healthy gene from the other parent.

People with HeFH have a 50% chance of passing the defective gene (and by extension, FH) on to their offspring. If both parents have HeFH, there is an increased chance of their child having HeFH, or the child could have HoFH.

Small global subpopulations have a higher incidence rate of HeFH, including:

  • Lebanese Christians (one in 85)
  • Afrikaners in South Africa (one in 72 to one in 100)
  • French Canadians (1 in 270)
  • Ashkenazi Jews originating from Lithuania (one in 67)

Is FH Caused by Lifestyle Habits?

FH is a lifelong, genetic condition apparent at birth. Unlike many cases of high cholesterol, FH is not caused by lifestyle choices.

Healthy lifestyle choices such as diet and exercise can help manage FH and prevent complications from it such as heart disease. Usually, this approach is accompanied by medication.

Diagnosis

HeFH is significantly underdiagnosed, particularly in children.

Only about 10%–20% of people with FH are aware they have the condition.

Often, a person may be unaware they have FH until they begin experiencing heart problems or have a heart attack at a young age.

For this reason, family history records are important. People who have a family history of early-onset heart disease or heart attacks (before age 55 in men and before age 65 in women) should look into the possibility of HeFH. This is especially important if the person also has high or borderline high LDL cholesterol levels.

F+H= FH

The FH Foundation suggests the following equation for assessing the risk of FH:

Family history of early heart disease + High LDL cholesterol = Familial Hypercholesterolemia

Early detection of HeFH is important for preventing complications.

If you have a family history of FH or of early-onset heart disease or heart attack:

  • Have your cholesterol levels checked regularly, ideally at least once a year, even if you are still young.
  • Have your children's cholesterol checked at age 2 and monitor it.
  • Watch for symptoms of FH in yourself and your children.

HeFH can be diagnosed in a number of ways.

Physical Exam

A physical exam may be performed if HeFH is suspected, or it may done as part of routine screenings, such as an annual physical.

During a physical exam, the healthcare provider may:

  • Ask about a personal and family history of FH, heart problems, high cholesterol, and other related questions
  • Perform a physical examination of the body to look for signs such as fatty skin deposits
  • Ask about other symptoms, such as chest pain
  • Make referrals or order tests if necessary

Do Children Need to Be Checked for High Cholesterol?

Even if there is no family history of FH, or known risk factors for the child, all children should have their cholesterol levels checked between the ages of 9 and 11 and rechecked between ages 17 and 21.

Tests

Blood tests may be run to check cholesterol levels. HeFH may be considered if:

  • Total cholesterol (a measurement of the total amount of cholesterol in your blood, both LDL and HDL, or “good” cholesterol) is above 300 mg/dL (250 mg/dL in children)
  • LDL is above 200 mg/dL (150 mg/dL in children)

Other tests that may be performed include:

  • Studies of cells called fibroblasts to see how well the body absorbs LDL cholesterol
  • Genetic testing to look for the presence of the faulty gene associated with FH

Treatment

There is no cure for HeFH. The goal of treatment is to manage LDL levels, and reduce the risks of complications such as heart disease. Treatment for HeFH is lifelong.

Treatment for HeFH is multifaceted and usually includes further testing and monitoring, medication, and lifestyle changes.

Further Testing

After a diagnosis of HeFH, other tests and screenings may be performed before treatment starts. This may include:

  • Pretreatment lipid values (tests that check for different cholesterol measurements)
  • Lipoprotein(a) levels (an additional risk factor for coronary artery disease)
  • Tests to look for or exclude other conditions that can affect lipid levels (such as kidney disease, uncontrolled hypothyroidism, acute myocardial infarction, and infection)
  • A consultation with a lipid specialist or a healthcare provider with expertise in FH
  • A consultation for medical genetics or genetic counseling
  • In children, noninvasive imaging procedures, such as a carotid intima-media thickness test (CIMT) to look for thickening of the carotid artery

Medication

HeFH can rarely be managed without medication.

The most prescribed medications are statins. Statin medications help control cholesterol levels and help lower the risk of heart attack and stroke.

Most adults with HeFH require high-intensity statin therapy. Children with HeFH should be started at the lowest recommended dose and increased as necessary.

 Statin drugs include:

  • Mevacor (lovastatin)
  • Pravachol (pravastatin)
  • Zocor (simvastatin)
  • Lescol (fluvastatin)
  • Lipitor (atorvastatin)
  • Livalo (pitivastatin)
  • Crestor (rosuvastatin)

Other medications that may be prescribed to lower cholesterol include:

  • Bile acid-sequestering resins
  • Ezetimibe
  • Fibrates (such as gemfibrozil or fenofibrate)
  • Nicotinic acid
  • PCSK9 inhibitors, such as Praluent (alirocumab) and Repatha (volocumab)

Lifestyle Changes

While nonfamilial high cholesterol can often be resolved or controlled with lifestyle changes, most people with HeFH cannot successfully treat their condition with healthy lifestyle habits alone.

Lifestyle changes and healthy habits are still an important facet of treatment for HeFH.

Some lifestyle practices that help to manage HeFH include:

Examine Your Diet

  • Reduce fat intake, making it account for less than 30% of total calories.
  • Limit saturated fats, such as animal products like red meat and dairy.
  • Eliminate trans fats, which are found in foods made with hydrogenated or partially hydrogenated oils, like margarine, packaged snacks, fast food, and baked goods.
  • Choose leaner cuts of meat.
  • Switch to low-fat dairy products.
  • Avoid egg yolks and organ meat, such as liver.
  • Snack on fruits and vegetables.
  • Get plenty of soluble fiber, which is found in fruits and vegetables, whole grains, beans, nuts, and seeds.

Get Active

Exercise regularly, and aim for the American Heart Association's recommended 150 minutes or more of moderate-intensity physical activity or 75 minutes of vigorous activity each week.

These activities can be done in more manageable 10- or 15-minute sessions each day.

These exercises may include:

  • Walking
  • Jogging
  • Swimming
  • Bicycling
  • Aerobics classes
  • Dancing
  • Anything that gets your heart rate up to the right level for aerobic exercise

Adding strength training and stretching exercises to aerobic exercises can help strengthen the heart, lower blood pressure, increase muscle mass, and improve circulation.

Find and Maintain a Healthy Target Weight

Discuss with your healthcare provider if weight loss is necessary beyond the measures taken for a healthy lifestyle, such as eating and exercise habits.

If so, make a plan to achieve this weight loss in a healthy way, under the guidance of a healthcare provider or dietitian.

Do Not Smoke

If you don't smoke, don't start, and limit exposure to secondhand smoke.

If you do smoke, discuss ways to stop with your healthcare provider.

LDL Apheresis

This procedure is similar to dialysis, a process of filtering blood through a machine to remove impurities or, in this case, LDL. It is used for people who have extremely high LDL cholesterol.

It is performed every few weeks to remove cholesterol from the blood.

During the procedure, blood or plasma is removed from the body and the extra LDL cholesterol is removed using special filters. The blood plasma is then returned to the body.

What Is Cascade Screening?

Cascade screening means that when one person is diagnosed with FH, their immediate family members are also tested.

Because FH is inherited, it is likely that other family members also have the condition.

Early diagnosis allows for treatment to start before symptoms or complications arise.

Prognosis

Untreated, HeFH increases the risk of early-onset heart disease and the complications that come with it.

Fortunately, treatments for HeFH are often very effective, especially when started early, before heart disease or cardiovascular events occur.

It is important to recognize that treatment for HeFH is lifelong. Closely follow the treatment plan developed between you and your healthcare provider.

Take all medication as directed, carefully monitor your LDL cholesterol levels, and attend all follow-up appointments to make sure your treatment plan is effective and continues to be effective.

A Word From Verywell

It can be frightening to learn that you have a condition that causes an increased risk of heart disease. While it sounds scary, there are measures that can be taken to lower this risk and help you lead a heart-healthy life.

If you have a family history of early-onset heart problems, heart attack, or high cholesterol, book an appointment with your healthcare provider to have your cholesterol checked, even if you aren't showing symptoms of HeFH. If you have children over age 2, have them screened as well.

If you have high LDL cholesterol or have other signs of HeFH, speak with your healthcare provider about screening for HeFH.

If you receive an HeFH diagnosis, don't panic. Discuss treatment options with your healthcare provider and start making positive lifestyle changes. A good treatment and management plan goes a long way to keeping HeFH under control and living a long, healthy life.

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12 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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