What You Need to Know About Homozygous Familial Hypercholesterolemia

This article is for people who have homozygous familial hypercholesterolemia (HoFH) or anyone who wants to learn more about it. The goal of this activity is to help inform people who have or are at risk of having HoFH about how it happens and how it can be managed.

You will learn about:

• What HoFH is

• How it happens and how it’s linked to heart disease

• Ways HoFH can be treated

• Living a healthier life with HoFH

• Talking to your doctor about HoFH

HoFH, or homozygous familial hypercholesterolemia, is a type of familial hypercholesterolemia (FH). FH is a serious disease that causes dangerously high levels of low-density lipoprotein (LDL) cholesterol or “bad” cholesterol.

There are 2 types of FH -- heterozygous FH (HeFH) and homozygous FH (HoFH). HoFH is less common and more severe than HeFH.

HoFH is a genetic disease that you were born with. This happens when both of your parents have a form of FH -- either HeFH or HoFH -- and then passed it on to you. Chances are, your sibling(s) and children might also have a form of FH.

When you have HoFH, you have extremely high LDL cholesterol (above 400 mg/dL) in your body right from the start, even before you were born. Having this lifelong exposure to such high levels of bad cholesterol can lead to other health problems, like early heart disease.

For anyone with high cholesterol, your chances of developing heart disease are increased. Cholesterol builds up in the blood vessels throughout your body and is called plaque. Plaque can then stop blood from flowing to your heart, causing a heart attack. Plaque can also break off from a blood vessel and form a blood clot, which can travel to your brain causing a stroke.

Because people with HoFH have very high cholesterol before birth, they develop health problems earlier in life. If HoFH is not treated, it can lead to problems like a heart attack, stroke, heart valve disease, and peripheral artery disease (high cholesterol in your arms and legs), even in children as young as 5 years old.

Your liver plays an important role in making cholesterol and then removing extra cholesterol from your blood. Cells in your liver have LDL receptors (LDLR) on them which help them take in and remove extra LDL cholesterol that is in your blood.

When you have HoFH, you have 2 mutations (or changes in your genes), 1 from each parent. These mutations affect the number of LDL receptors there are on your liver cells and how well they work. This makes it hard for the cells to remove extra LDL cholesterol from your blood. So it can build up in your blood over time, starting from a young age.

With medicines, it can be possible to bring your cholesterol down to a healthier level. Medicines that are commonly used to treat high cholesterol that can also be used in people who have HoFH include:

• Statins -- such simvastatin or atorvastatin -- a pill taken once a day. Side effects may include pain and muscle aches

• Cholesterol absorption inhibitor -- such as ezetimibe -- a pill taken once a day. Side effects may include cough and headache

• Bile acid sequestrants -- such as colesevelam and colestipol -- multiple pills or powder mixed in a beverage. Side effects may include stomach-related issues and dizziness

• PCSK9 inhibitors -- such as evolocumab and alirocumab -- an injection taken every 2 or 4 weeks. Side effects may include pain or redness where the shot was given and cold or flu symptoms

• Adenosine triphosphate-citrate lyase (ACL) inhibitor -- such as bempedoic acid -- a pill taken once a day. Side effects may include body pain and cold or flu symptoms

There are also medicines specifically for people with HoFH:

• Angiopoietin-like 3 (ANGPTL3) monoclonal antibody -- such as evinacumab -- an infusion taken once a month at a hospital or clinic or at home. Side effects may include dizziness and cold or flu symptoms

• Microsomal triglyceride transfer protein (MTP) inhibitor -- such as lomitapide -- a pill taken once a day. Side effects may include stomach issues

There is also a procedure called apheresis which is done once a week or every other week to help remove excess cholesterol from your blood.

When you have HoFH, it's important to maintain a heart healthy lifestyle by:

• Eating a healthy diet with plenty of fruits, vegetables, and grains

• Getting at least 150 minutes of physical activity in a week (or 30 minutes for 5 days)

• Maintaining a healthy weight with the right portion sizes and healthy snacks

• Quitting smoking

You can also talk to your family about getting tested to see if they might have HoFH or HeFH and should start treatment early.

HoFH is treated in a step-wise approach. You’ll start with a statin, and then your doctor will add on more medicines.

You will have to take many medicines together to treat HoFH. This is because statins, ezetimibe, and PCSK9 inhibitors all work in the body through your liver LDL receptors and they do not work as well in people with HoFH. But medicines like evinacumab and lomitapide are typically added on and can help because they do not need the LDL receptors to work. 

With so many options available, it is important to have a careful discussion with your doctor and a lipid specialist about which medicines are right for you.

Remember, HoFH is a lifelong condition, which means that you will have to take your medicines as directed by your doctor for a long time. If you have any questions or any side effects, be sure to let your doctor know.

You have successfully completed the program: What You Need to Know About Homozygous Familial Hypercholesterolemia.

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Genetic Counseling for Familial Hypercholesterolemia

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