What are the other Names for this Condition? (Also known as/Synonyms)

• Autosomal Dominant Hypercholesterolemia
• Heterozygous Familial Hypercholesterolemia
• Hypercholesterolemic Xanthomatosis

What is Familial Hypercholesterolemia? (Definition/Background Information)

• Familial Hypercholesterolemia (FH) is a common inherited condition in which the body is unable to remove low-density lipoprotein cholesterol (bad cholesterol) from the bloodstream
• This results in high levels of cholesterol, which damages the walls of the arteries, causing atherosclerosis (hardening and narrowing of arteries) and heart attacks, at an early age

Who gets Familial Hypercholesterolemia? (Age and Sex Distribution)

• Familial Hypercholesterolemia is a serious medical condition that begins at birth. The inheritance pattern is the same for both males and females
• Ethnic groups, such as the French Canadians, the Finns, the Lebanese, the Ashkenazi Jews, and the Africans in South Africa, have an increased rate of mutation. Hence, FH is more common among these groups

What are the Risk Factors for Familial Hypercholesterolemia? (Predisposing Factors)

The risk factors for Familial Hypercholesterolemia include:

• Any individual, who has a parent with FH is at risk
• Individuals belonging to certain specific ethnic groups, such as the French Canadians, the Finns, the Lebanese, the Ashkenazi Jews, and the Africans in South Africa

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one's chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Familial Hypercholesterolemia? (Etiology)

• Familial Hypercholesterolemia is caused by mutation (defective gene) in the LDL receptor gene (LDLR) on chromosome 19. The defect prevents the body from removing LDL cholesterol from the bloodstream. The disorder is autosomal dominant, meaning that an individual can have the condition, even if only one parent has the mutated gene
• Cholesterol is normally removed from the blood by the liver, using Low Density Lipoprotein (LDL) receptors. Each individual has two genes that are responsible for making the LDL receptors; one received from their father and the other from the mother
• In a person with Heterozygous FH, an abnormal gene is passed on from one parent (who has FH) and a normal gene from the other parent (who does not have FH). Therefore, one half of the LDL receptors do not function properly, while the other half are normal
• Since, half the receptors do not remove the cholesterol normally, blood cholesterol levels increase. This result in consistently high levels of LDL in the blood, leading to atherosclerosis (narrowing of arteries) at an early age, causing heart attacks at a young age. There is also an increased deposit of cholesterol in other tissues, like the skin and tendons
• Rarely, both parents may pass a defective gene to the child. When this occurs, the condition is called Homozygous FH. The increase in cholesterol levels is much more severe in such cases. This greatly increases the risk for heart attacks and heart diseases, at a very early age, like even during childhood

What are the Signs and Symptoms of Familial Hypercholesterolemia?

Some of the signs and symptoms of Familial Hypercholesterolemia are:

• Chest pain (angina) and heart attacks, from heart disease
• Atherosclerosis (hardening and narrowing of the arteries)
• Fatty yellowish skin deposits (called xanthomas) over the elbows, buttocks, knees, and tendons
• Cholesterol deposits in the eyelids (xanthelasmas), and around the corneas (corneal arcus)
• High cholesterol levels
• Stroke
• Peripheral vascular disease (narrowing of the arteries in legs), which may cause pain during walking that is relieved by rest

Families with Familial Hypercholesterolemia often have a pattern of individuals in their 20’s, 30’s, 40’s, or 50’s, with very high cholesterol levels that lead to a heart attack or heart disease.

How is Familial Hypercholesterolemia Diagnosed?

Familial Hypercholesterolemia is diagnosed by physical examination, medical and family history evaluation, and through blood tests.

• Physical exam: The physical exam helps identify any types of fatty deposits or lesions, which have developed as a result of the elevated cholesterol
• Blood tests: Blood tests are used to determine the cholesterol levels. Individuals from families with a strong history of early heart attacks should have blood tests taken, to determine their lipid levels

The results may indicate high levels of total cholesterol and LDL cholesterol:

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: Normal results are below 150 mg/dL

Other diagnostic tests include:

• Genetic testing must be done to establish presence of the defective gene
• LDL receptor analysis can be done to identify the specific LDL receptor defect

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Familial Hypercholesterolemia?

In Familial Hypercholesterolemia, cholesterol can build up in the wall of the blood vessels and over time can lead to fatal heart attacks, stroke, and blood vessel disease. The following are the possible complications:

• Heart attack at a young age
• Heart disease
• Stroke 
• Aortic aneurysm rupture, often causing sudden death

Individuals, who have one abnormal copy (heterozygous) of the LDLR gene, have premature cardiovascular disease at the age of 30 to 40 years. Individuals, who have two abnormal copies (homozygous), have severe cardiovascular disease during their childhood.

How is Familial Hypercholesterolemia Treated?

Familial Hypercholesterolemia is managed using a suitable diet and medication. Often, a combination of both is needed to successfully reduce the cholesterol quantity and delay the onset of heart disease or a heart attack.

Lifestyle and dietary changes: These include reducing total fat intake to less than 30% of the total calorie intake, which is done by:

• Reducing the amount of meats, which include beef, chicken, pork, lamb, etc.
• Elimination of coconut and palm oil
• Interchanging full-fat dairy products with low-fat ones
• Eliminating butter, whole milk, and fatty cheese
• Limiting the consumption of egg yolks
• Weight loss, if the individual is overweight
• Regularly exercising

Medications: If lifestyle changes are not adequate, then medications are used to reduce the cholesterol quantity. Statins are the most common drugs used to reduce LDL cholesterol. The goal of the treatment is to reduce the risk of atherosclerotic heart disease. Other cholesterol-lowering drugs include:

• Bile acid-sequestering resins
• Ezetimibe
• Nicotinic acid
• Fibrates

Those who inherit only one copy of the defective gene (heterozygous) respond well to diet changes combined with statin drugs. However, individuals who inherit two copies of the defective genes (homozygous) are resistant to treatment.

Individuals with severe forms of FH disorder may undergo a treatment called extracorporeal apheresis. Blood or plasma is removed from the body and special filters are used to remove the extra LDL-cholesterol. The filtered blood plasma is then returned to the body. This is a very effective treatment measure.

Newer medications to alter the effects of abnormal proteins using RNA interference (RNAi) and other molecular technologies are in various stages of development and commercialization. The medical provider may help with information on advancements in new treatment methods.

How can Familial Hypercholesterolemia be Prevented?

• Familial Hypercholesterolemia is a genetic disease; the only way to prevent it is to get a genetic counseling prior to conception. If an individual has FH, then their children have a 50% chance of inheriting the condition
• In an individual who already has the disease, the key to longer life is in controlling the cholesterol levels. A diet, low in cholesterol and saturated fat, and rich in unsaturated fat, may help to control cholesterol levels
• If Familial Hypercholesterolemia is detected early, the risk of heart disease may be prevented or delayed by:
  • Quitting smoking
  • Exercising regularly
  • Eating a healthy diet
  • Using proper medications

What is the Prognosis of Familial Hypercholesterolemia? (Outcomes/Resolutions)

• The outcome with Familial Hypercholesterolemia depends on the lifestyle modifications and on the proper intake of prescribed medications. These changes can reduce the risk of heart disease significantly. Diet changes, exercise, and medications can lower the cholesterol levels for those with milder form of this disorder and may significantly delay a heart attack
• Men and women with FH typically are, at an increased risk of early heart attacks. Untreated males often develop symptoms of heart disease in their early forties, females in their early fifties
• Individuals, who inherit the defective gene from both their parents (Homozygous FH), are at greater risk for heart attack, before the age of 30. The outcome may be poor in such cases

Additional and Relevant Useful Information for Familial Hypercholesterolemia:

• Heterozygous Familial Hypercholesterolemia occurs as an autosomal dominant pattern, affecting 1 in 500 individuals
• Homozygous FH occurs with a lot less frequency (estimated incidence is about 1 in a million)
• In rare cases, when medical treatment fails, surgical treatment (like liver transplant) may be necessary in Homozygous FH