Understanding Homozygous Familial Hypercholesterolemia: Causes, Symptoms, and Treatment Options

Creator: Doctronic
Published: 2023-11-30

Medically reviewed by Jerome Albert Ecker | MD, Assistant Professor of Medicine, Duke University - Durham, NC on November 30th, 2023.

Key Takeaways

This ultra-rare condition affects only 1 in 160,000-300,000 people worldwide and occurs when both parents carry defective LDLR, APOB, or PCSK9 genes, causing cholesterol levels to skyrocket to 600-1,200 mg/dL.
Physical signs typically appear in childhood and include yellow fatty deposits (xanthomas) on knuckles, elbows, and Achilles tendons, plus white corneal rings visible around the iris by age 10.
Without treatment, heart attacks commonly occur before age 20, with some patients experiencing coronary artery disease as early as age 2-5 years due to accelerated atherosclerosis.
LDL apheresis—a dialysis-like procedure that filters cholesterol from blood—must be performed every 1-2 weeks and can reduce cholesterol by 60-80% per session.
Combination therapy with maximum-dose statins (80mg atorvastatin), PCSK9 inhibitors, and ezetimibe can achieve 50-70% cholesterol reduction, though levels often remain dangerously elevated above 300 mg/dL.

Homozygous familial hypercholesterolemia is a genetic disorder that affects the body's ability to remove LDL "bad" cholesterol from the blood. This condition can lead to extremely high cholesterol levels, increasing the risk of developing heart disease at an early age. While there is no cure, various treatment options are available to help manage the condition and reduce the risk of complications.

What Causes Homozygous Familial Hypercholesterolemia?

Homozygous familial hypercholesterolemia is an inherited condition caused by a faulty gene that affects the liver's ability to remove LDL cholesterol from the blood. In a healthy individual, the liver uses particles called LDL receptors to attach to LDL cholesterol and remove it from the bloodstream. However, in people with this disorder, the faulty gene prevents the LDL receptors from working properly, leading to a buildup of cholesterol in the blood.

Symptoms of Homozygous Familial Hypercholesterolemia

The main sign of homozygous familial hypercholesterolemia is extremely high levels of total cholesterol and LDL cholesterol. Some individuals may have a total cholesterol level of 600 points or higher, compared to the recommended level of less than 200. Other symptoms may include:

Yellow, waxy patches on the skin (xanthomas) over the elbows, knees, and buttocks
Yellowish fat deposits (xanthelasmas) in the eyelids
Gray or white circles around the cornea (the clear front part of the eye)
Chest pain (angina)
Rapid heartbeat
Shortness of breath

Diagnosing Homozygous Familial Hypercholesterolemia

To diagnose homozygous familial hypercholesterolemia, your doctor will perform a physical exam and order blood tests to check your cholesterol levels. They may also ask about your family history of high cholesterol and any symptoms you may be experiencing. In some cases, a blood test to look for the abnormal gene that causes this condition may be recommended. Your doctor might also suggest testing close relatives to see if they have the condition.

Understanding Homozygous Familial Hypercholesterolemia: Causes, Symptoms, and Treatment Options

Treatment Options for Homozygous Familial Hypercholesterolemia

The goal of treatment is to lower LDL cholesterol levels and reduce the risk of heart disease. Treatment typically involves a combination of lifestyle changes and medications. Your doctor may recommend:

1. Heart-healthy Diet

A modified Mediterranean-inspired diet may be helpful. Adopting a diet low in saturated fat, cholesterol, and sugar can help manage cholesterol levels. Focus on consuming fruits, vegetables, whole grains, nuts, legumes, seafood, lean poultry, and low-fat dairy. Limit your total fat intake to 30% or less of your daily calories.

2. Medications

Due to the extremely high cholesterol levels associated with homozygous familial hypercholesterolemia, your doctor may prescribe high doses of statin drugs, which work by preventing the liver from producing cholesterol. Other medications, such as ezetimibe (Zetia), PCSK9 inhibitors like alirocumab (Praluent) and evolocumab (Repatha), or lomitapide (Juxtapid), may be used in combination with statins to further reduce cholesterol levels.

3. Apheresis

If medications are not effective, your doctor may recommend apheresis, a procedure that removes cholesterol from the blood. During apheresis, blood is removed through a catheter, and LDL cholesterol is filtered out before the blood is returned to the body. This procedure takes several hours and needs to be performed regularly.

4. Liver Transplant

In rare cases where other treatments are ineffective, a liver transplant may be necessary. A new liver with normal LDL receptors can help remove bad cholesterol from the blood. However, this is a major surgery that requires a long recovery time and lifelong use of immunosuppressant medications to prevent organ rejection.

Living with Homozygous Familial Hypercholesterolemia

Managing homozygous familial hypercholesterolemia is a lifelong commitment. In addition to following your prescribed treatment plan, it's essential to adopt a healthy lifestyle. This includes regular exercise, stress management, maintaining a healthy weight, and avoiding smoking and excessive alcohol consumption. Regular check-ups with your healthcare provider are crucial to monitor your condition and adjust treatment as needed.

Seeking emotional support from family, friends, and support groups can be beneficial when coping with this chronic condition. Organizations like the FH Foundation provide resources, information, and support for individuals and families affected by familial hypercholesterolemia.

For more information on homozygous familial hypercholesterolemia, consult the following resources:

The Bottom Line

This genetic condition requires immediate, aggressive treatment to prevent fatal heart disease in childhood or young adulthood. Early diagnosis and combination therapy including regular apheresis procedures can significantly extend life expectancy. If you notice unusual fatty deposits on your child's skin or have a family history of early heart disease, Doctronic can help connect you with specialists quickly.