FAMILIAL HYPERCHOLESTEROLEMIA

TYPES

Familial hypercholesterolemia (FH) can be categorized into different types based on the severity of the condition and the specific genetic mutations involved. The two main types of FH are:

1. Heterozygous FH (HeFH): This is the most common type of FH, accounting for about 95% of cases. In HeFH, an individual inherits one mutated copy of the gene responsible for regulating cholesterol metabolism (typically the LDL receptor gene) from one parent. This results in moderately elevated LDL cholesterol levels. HeFH can vary in severity, with some individuals experiencing mild symptoms while others may have more significant cholesterol buildup and increased risk of cardiovascular disease.

2. Homozygous FH (HoFH): Homozygous FH is a rare and more severe form of FH, accounting for about 1% of cases. In HoFH, an individual inherits two copies of the mutated gene (one from each parent), leading to severely elevated LDL cholesterol levels. HoFH is associated with a higher risk of cardiovascular disease at an early age. The buildup of cholesterol is more extensive and treatments often need to be more aggressive to manage the condition.

SYMPTOMS

Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated levels of cholesterol in the blood. While FH often does not present with specific symptoms in childhood, it can lead to early signs of cardiovascular disease in adulthood. Here are some symptoms and manifestations commonly associated with FH:

1. Xanthomas: These are fatty deposits that can develop on tendons, particularly around the elbows and knees. Xanthomas may appear as small, firm, yellowish bumps or nodules under the skin.

2. Xanthelasmas: These are cholesterol deposits that form on the eyelids. They usually appear as yellowish patches or plaques and may be a sign of high cholesterol levels.

3. Arcus corneae: This refers to a grayish-white or yellowish ring that forms around the outer edge of the cornea of the eye. It is caused by lipid deposits and can be an indicator of high cholesterol levels.

4. Premature cardiovascular disease: FH significantly increases the risk of developing heart disease, including coronary artery disease, heart attacks, and strokes at a younger age. Individuals with FH may experience symptoms such as chest pain, shortness of breath, and palpitations.

DIAGNOSIS

The diagnosis of familial hypercholesterolemia (FH) typically involves a combination of clinical evaluation, family history assessment, and laboratory testing. Here are some key steps in diagnosing FH:

1. Clinical evaluation: A healthcare professional, such as a lipid specialist or genetic counselor, will conduct a thorough evaluation of your medical history, family history, and physical examination. They will ask about any symptoms you may be experiencing and assess your risk factors for FH.

2. Family history assessment: FH is an inherited condition, so having a family history of high cholesterol or premature heart disease is an important clue. The healthcare professional will ask about your family’s medical history, specifically looking for relatives who have had high cholesterol, heart attacks, strokes, or other cardiovascular problems at a young age.

3. Laboratory testing: Blood tests will be performed to measure your cholesterol levels, including total cholesterol, LDL cholesterol (often referred to as “bad” cholesterol), HDL cholesterol (often referred to as “good” cholesterol), and triglycerides. Elevated LDL cholesterol levels are a key characteristic of FH.

4. Genetic testing: In some cases, genetic testing may be recommended to confirm a diagnosis of FH. Genetic testing can identify specific gene mutations associated with FH, such as mutations in the LDL receptor gene, ApoB gene, or PCSK9 gene. However, it’s important to note that not all cases of FH can be identified through genetic testing, as there may be other genetic factors involved.

5. Additional testing: Depending on the specific situation, additional tests may be performed to assess cardiovascular health, such as an electrocardiogram (ECG) or stress test, to evaluate the function of the heart and detect any signs of heart disease.

TREATMENT

The treatment of familial hypercholesterolemia (FH) aims to lower cholesterol levels, reduce the risk of cardiovascular complications, and improve overall heart health. Here are some common treatment approaches for FH:

1. Lifestyle modifications: Adopting heart-healthy lifestyle habits can have a significant impact on managing cholesterol levels. This includes eating a balanced diet low in saturated and trans fats, engaging in regular physical activity, maintaining a healthy weight, avoiding tobacco smoke, and limiting alcohol consumption.

2. Medications: Medications are often prescribed to individuals with FH, especially if lifestyle modifications alone are not sufficient to control cholesterol levels. Statins are the most commonly prescribed medications for FH and work by reducing the production of cholesterol in the liver. Other medications, such as ezetimibe, bile acid sequestrants, and PCSK9 inhibitors, may be used in combination with or as an alternative to statins, depending on the individual’s specific situation.

3. Lipid apheresis: In severe cases of FH or when cholesterol levels cannot be adequately managed with medications alone, lipid apheresis may be considered. This is a procedure that removes cholesterol from the blood, similar to dialysis. During lipid apheresis, the blood is passed through a machine that filters out LDL cholesterol, returning the blood back to the body.

4. Regular monitoring: Individuals with FH need regular monitoring of their cholesterol levels and overall cardiovascular health. This involves periodic blood tests to measure cholesterol levels, as well as monitoring other risk factors, such as blood pressure and blood sugar levels. Regular follow-up visits with a healthcare professional are important to assess the effectiveness of treatment and make any necessary adjustments.