Type IIa Hyperlipidaemia

Type IIa hyperlipidaemia is a genetic condition that causes dangerously high levels of cholesterol in the blood from birth, significantly increasing the risk of heart disease and stroke at a young age.

Table of contents

• What is Type IIa Hyperlipidaemia?
• Other Names for This Condition
• What Causes Type IIa Hyperlipidaemia?
• How Common is Type IIa Hyperlipidaemia?
• Signs and Symptoms
• Testing and Diagnosis
• Treatment Options
• Possible Complications
• Importance of Family Screening

What is Type IIa Hyperlipidaemia?

Type IIa hyperlipidaemia, also known as familial hypercholesterolemia, is a health condition passed down through families that affects how the body handles fats^[1]. People with this condition have very high levels of a specific type of cholesterol known as low-density lipoprotein cholesterol (LDL-C), which is often called “bad cholesterol”^[4].

The high cholesterol levels result from a gene mutation and can lead to early onset of heart disease^[4]. This condition is characterized by significantly elevated LDL-C that leads to atherosclerotic plaque deposition (cholesterol buildup) in the coronary arteries and the main artery near the heart at an early age^[1]. This increases the risk of premature cardiovascular events such as chest pain and heart attacks, though stroke occurs more rarely^[1].

In the classification system developed by Fredrickson, Type IIa is the most common type of familial hypercholesterolemia^[5]. People who inherit this condition from both parents typically develop the disease during childhood and have more severe symptoms than those who inherit it from one parent^[4].

Other Names for This Condition

Fredrickson type IIa hyperlipoproteinemia, Familial hypercholesterolemia type 1, Hyperlipoproteinemia Type IIa, Hyper-beta-lipoproteinemia, Hypercholesterolemic xanthomatosis familial, LDLR-Related Familial Hypercholesterolemia

What Causes Type IIa Hyperlipidaemia?

Type IIa hyperlipidaemia is caused by genetic mutations that are passed down from parents to their children^[1]. The condition demonstrates an autosomal dominant inheritance pattern, meaning that on average 50% of children of an affected parent will have the disease passed on to them^[6].

The main genetic causes involve defects in three specific genes. Changes in the LDL receptor gene (LDLR), also known as “classic FH,” cause 80% to 90% of these cases^[4]. More than 1,600 mutations in the LDLR gene that cause high cholesterol have been identified^[4]. In some rare cases, mutations in the APOB and PCSK9 genes can also lead to high cholesterol^[4].

The APOB gene creates a major protein in LDL cholesterol that connects with LDL receptors. Any mutation here might result in faulty protein, leading to poor interaction between LDL particles and LDL receptors, which in turn results in impaired removal of cholesterol from the blood^[4].

The PCSK9 gene creates a protein that regulates the lifespan of LDL receptors. In case of a mutation, it might result in excess function, leading to high cholesterol^[4].

These mutations make it impossible for patients with Type IIa hyperlipidaemia to remove excess low-density lipoproteins from the bloodstream^[6]. As a result, cholesterol accumulates in the bloodstream and can ultimately build up in the walls of the arteries^[6].

How Common is Type IIa Hyperlipidaemia?

Familial hypercholesterolemia is the most common inherited genetic disorder in humans^[4]. It affects about one in 300 people^[4]. This condition is 18 times more common in people with a certain heart disease and 21 times more common in people with early onset heart disease^[4].

Certain groups of people have a higher rate of this disorder, including Dutch Afrikaners, French Canadians, Ashkenazi Jews, Christian Lebanese, and some Tunisian groups^[4].

Unfortunately, many cases of familial hypercholesterolemia go unnoticed and are not treated effectively^[4]. That’s why it’s so crucial to diagnose and manage this condition early to avoid early deaths^[4].

Signs and Symptoms

Many people with Type IIa hyperlipidaemia may not have visible symptoms, especially in the early stages. However, the condition can cause several distinctive physical signs as cholesterol builds up in the body over time^[1].

Cholesterol deposits called xanthomas may be visible in the tendons. These are painless soft tissue masses that appear as yellowish bumps, most commonly occurring in the Achilles tendons (the large tendon at the back of the ankle) or tendons of the hands^[1][6]. They are usually present on both sides of the body and worsen with age as a result of extremely high cholesterol levels^[1].

Xanthelasmas are yellowish, waxy deposits that can occur around the eyelids^[1][6]. These are well-defined, flat or slightly raised yellowish growths^[6].

Individuals with Type IIa hyperlipidaemia may develop corneal arcus, which appears as a white, gray, or blue opaque ring in the edge of the cornea (the clear front part of the eye) as a result of cholesterol deposition^[1]. People with this condition typically develop this at a younger age than those without familial hypercholesterolemia^[1].

The most serious concern is accelerated atherosclerosis (faster buildup of fatty deposits in arteries), which is caused by very high levels of LDL cholesterol^[6]. This can lead to early-onset coronary artery disease, presenting as early as childhood in some cases^[1]. Patients with familial hypercholesterolemia may have a heart attack before age 20^[6].

Testing and Diagnosis

A detailed family history is an important key to diagnosing Type IIa hyperlipidaemia^[11]. Healthcare professionals will be interested to know if your siblings, parents, aunts, uncles, or grandparents ever had high cholesterol levels or heart disease, especially during childhood^[11].

During the physical exam, your healthcare team will usually check for cholesterol deposits that may occur in the skin around the hands, knees, elbows, and eyes. Tendons in the heel and hand may be thickened, and a gray or white ring may develop around the edge of the eye^[11].

Your healthcare team will order blood tests to check your cholesterol levels^[11]. Adults who have familial hypercholesterolemia usually have LDL cholesterol levels over 190 mg/dL or have cholesterol levels that stay high even when on cholesterol-lowering treatments^[11]. Children who have the condition often have LDL cholesterol levels over 160 mg/dL^[11]. In more serious cases, LDL cholesterol levels can be over 500 mg/dL^[11].

A genetic test can confirm familial hypercholesterolemia, but it’s not always necessary for diagnosis, which is usually based on physical symptoms and family history^[4][11]. About 30 to 50% of patients with symptoms of high cholesterol do not have a detectable gene defect^[4].

Treatment Options

Early detection of Type IIa hyperlipidaemia and aggressive management to lower the LDL cholesterol level helps in preventing or slowing the progression of coronary atherosclerosis^[5].

Treatment typically involves both lifestyle changes and medications. Lifestyle modifications are usually initiated before any drug therapy, particularly in patients who have no symptoms^[5]. These include weight reduction and a diet low in saturated fat and cholesterol^[5].

Statins are the main treatment for Type IIa hyperlipidaemia. These medications work to reduce the amount of cholesterol produced by the liver^[1]. High-potency statins at high doses have greater effectiveness in reduction of cardiovascular events than low potency statins or high-potency statins at low doses^[5].

Some people need additional medications beyond statins. These adjunct therapies can include niacin, bile acid sequestrants (medications that help remove cholesterol from the body), fibric acids, and ezetimibe (a medication that blocks cholesterol absorption)^[13].

For more severe cases that are difficult to treat, other options may be necessary. These can include lomitapide, mipomersen, PCSK9 inhibitors (newer injectable medications that help lower LDL cholesterol), or LDL cholesterol apheresis (a procedure that filters cholesterol from the blood), in addition to high-dose statins or other agents^[13].

Managing your cholesterol is a long-term effort^[2]. You’ll need to watch what you eat and exercise regularly. Most people will need to take prescription medication for life to keep their cholesterol levels under control.

Possible Complications

Type IIa hyperlipidaemia can be very serious if it’s not managed. As long as high cholesterol is untreated, plaque continues to accumulate inside blood vessels^[2]. Cholesterol buildup in the artery wall can lead to serious problems such as heart attacks and strokes in young adults and even children^[6].

The high cholesterol levels lead to atherosclerotic plaque deposition in the coronary arteries (the blood vessels that supply the heart) and the main artery near the heart at an early age^[1]. This increases the risk of premature cardiovascular events such as angina (chest pain) and heart attack^[1].

This can lead to a heart attack or stroke because blood has a hard time getting through blood vessels. This deprives the brain and heart of the nutrients and oxygen they need to function^[2].

Individuals with a more severe form of the condition, often as a result of inheriting defective genes from both parents, can present with very significant elevations in LDL-C (over 500 mg/dL), early-onset coronary artery disease (presenting as early as childhood in some), and calcific aortic valve disease (hardening of one of the heart valves due to calcium deposits)^[1].

Importance of Family Screening

Type IIa hyperlipidaemia is inherited and passed down through families^[6]. When one individual with this disease is diagnosed, it is important that all family members are screened for familial hypercholesterolemia^[6].

First-degree relatives (parents, siblings, and children) of a patient with familial hypercholesterolemia should be screened, so that other gene carriers can be identified and treated^[5]. Early detection allows for early intervention, which can significantly reduce the risk of cardiovascular complications.

The National Heart, Lung, and Blood Institute recommends that a person’s first cholesterol screening should occur between the ages of 9 and 11 and be repeated every five years after that^[11]. Earlier or more frequent screenings may be suggested for families with a history of childhood heart disease^[11].

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