Familial Hypercholesterolemia: Symptoms, Causes, Treatment

What are the symptoms of familial hypercholesterolemia?

Familial hypercholesterolemia (FH) is a genetic disorder characterized by high levels of low-density lipoprotein (LDL) cholesterol, often referred to as “bad” cholesterol, in the blood. This condition is caused by mutations in genes that are involved in the body’s ability to remove LDL cholesterol from the bloodstream. Symptoms of FH can vary, but may include:

1. High cholesterol levels: People with FH typically have significantly elevated levels of LDL cholesterol from a young age, often above 190 mg/dL.
2. Xanthomas: These are deposits of cholesterol that can form under the skin, typically around the eyes, on the elbows, knees, hands, or feet. Xanthomas appear as yellowish lumps or bumps.
3. Corneal arcus: A white or gray ring that forms around the cornea of the eye, which can be a sign of high cholesterol levels.
4. Heart disease: Individuals with FH have a much higher risk of developing heart disease at an early age compared to the general population.
5. Family history: FH is a genetic disorder, so a family history of high cholesterol or early heart disease is common.

It’s important to note that not everyone with FH will have noticeable symptoms, especially in the early stages. Therefore, screening for FH, particularly in individuals with a family history of high cholesterol or early heart disease, is important for early detection and management.

What are the causes of familial hypercholesterolemia?

Familial hypercholesterolemia (FH) is primarily caused by genetic mutations that affect the body’s ability to remove low-density lipoprotein (LDL) cholesterol from the bloodstream. There are several genes that, when mutated, can lead to FH. The most common genes associated with FH are:

1. LDLR gene: Mutations in the LDL receptor gene (LDLR) are the most common cause of FH. This gene provides instructions for making a protein that helps remove LDL cholesterol from the blood. Mutations in this gene can lead to reduced LDL receptor function, resulting in high levels of LDL cholesterol in the blood.
2. APOB gene: Mutations in the apolipoprotein B gene (APOB) can also cause FH. This gene provides instructions for making a protein that is involved in the binding and transport of LDL cholesterol. Mutations in this gene can lead to impaired LDL cholesterol clearance.
3. PCSK9 gene: Mutations in the proprotein convertase subtilisin/kexin type 9 gene (PCSK9) can cause a rare form of FH. This gene provides instructions for making a protein that regulates the number of LDL receptors on the surface of cells. Mutations in this gene can lead to increased levels of LDL cholesterol in the blood.

FH is inherited in an autosomal dominant pattern, which means that a person only needs to inherit one copy of the mutated gene from either parent to develop the disorder. If one parent has FH, each child has a 50% chance of inheriting the mutated gene and developing FH.

How is the diagnosis of familial hypercholesterolemia made?

The diagnosis of familial hypercholesterolemia (FH) is typically based on a combination of clinical evaluation, family history, and laboratory tests. The following are key steps in the diagnosis process:

1. Clinical evaluation: A healthcare provider will assess the individual’s medical history, including any family history of high cholesterol or early heart disease, as FH is a genetic disorder that tends to run in families.
2. Physical examination: A physical examination may be conducted to look for physical signs of FH, such as xanthomas (deposits of cholesterol under the skin) or corneal arcus (a white or gray ring around the cornea).
3. Cholesterol levels: Blood tests will be done to measure the levels of total cholesterol, LDL cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides. High levels of LDL cholesterol are a hallmark of FH.
4. Genetic testing: Genetic testing may be recommended to confirm a diagnosis of FH. This involves analyzing specific genes associated with FH, such as the LDLR, APOB, and PCSK9 genes, to look for mutations.
5. Family screening: Since FH is a genetic disorder that runs in families, screening family members of an individual diagnosed with FH may be recommended to identify other affected individuals.

It’s important to diagnose FH early to initiate appropriate treatment and reduce the risk of complications, such as heart disease. A diagnosis of FH may also prompt screening and management of other cardiovascular risk factors, such as high blood pressure and smoking.

What is the treatment for familial hypercholesterolemia?

The treatment for familial hypercholesterolemia (FH) aims to lower LDL cholesterol levels and reduce the risk of heart disease. Treatment options may include:

1. Lifestyle changes: Adopting a heart-healthy diet, exercising regularly, maintaining a healthy weight, and avoiding tobacco smoke are important for managing cholesterol levels and reducing the risk of heart disease.
2. Cholesterol-lowering medications: Statins are usually the first-line treatment for FH. These medications help lower LDL cholesterol levels by blocking a substance your liver needs to produce cholesterol. In some cases, other cholesterol-lowering medications such as ezetimibe or PCSK9 inhibitors may be prescribed.
3. Lipid apheresis: This procedure filters LDL cholesterol from your blood. It may be recommended for people with very high LDL cholesterol levels who haven’t responded adequately to other treatments.
4. Liver transplant: In rare cases of severe FH that do not respond to other treatments, a liver transplant may be considered. This is because the liver is the primary source of LDL cholesterol production in the body, and a transplant can replace the liver with one that does not have the genetic mutation causing FH.
5. Genetic counseling: FH is an inherited condition, so genetic counseling may be recommended for individuals with FH and their families. This can help individuals understand their risk of passing the condition to their children and explore options for family planning.

Treatment for FH is usually lifelong, and regular monitoring of cholesterol levels and cardiovascular health is important. Early diagnosis and aggressive treatment can help reduce the risk of heart disease and improve outcomes for individuals with FH.

What is the life expectancy of someone with familial hypercholesterolemia?

Familial hypercholesterolemia (FH) is a genetic disorder that affects the body’s ability to remove low-density lipoprotein (LDL) cholesterol, leading to high levels of LDL cholesterol in the blood. The life expectancy of individuals with FH depends on various factors, including the severity of the condition, the presence of other health conditions, and the effectiveness of treatment.

Untreated FH can lead to premature cardiovascular disease, which is a major cause of death in people with FH. Studies have shown that individuals with untreated FH tend to develop cardiovascular disease at an earlier age than the general population. For example:

• A study published in the New England Journal of Medicine found that individuals with untreated FH had a 30% risk of having a myocardial infarction (heart attack) before the age of 65.
• Another study published in the Journal of the American College of Cardiology found that untreated FH patients had a 45% risk of having a cardiovascular event (such as heart attack or stroke) before the age of 55.

However, with early diagnosis and treatment, it is possible to significantly reduce the risk of cardiovascular disease and improve life expectancy. Studies have shown that statin therapy, which is commonly used to treat FH, can reduce the risk of cardiovascular events by up to 80%.

In general, the life expectancy of individuals with FH who receive early and effective treatment is similar to that of the general population. For example:

• A study published in the Journal of Clinical Lipidology found that individuals with treated FH had a similar life expectancy to that of the general population.
• Another study published in the European Heart Journal found that treated FH patients had a significantly lower risk of cardiovascular events and mortality compared to untreated patients.

Overall, while FH can be a serious condition, early diagnosis and treatment can help to reduce the risk of cardiovascular disease and improve life expectancy.