Homozygous Familial Hypercholesterolemia

Welcome to our webpage dedicated to Homozygous Familial Hypercholesterolaemia. We hope you will find it useful.

To understand Homozygous Familial Hypercholesterolemia (HoFH), it is important to understand first Familial Hypercholesterolaemia in general.


Familial hypercholesterolaemia

Familial hypercholesterolaemia is a term used to describe a genetic lipid condition that causes high cholesterol. People with FH have an elevated level of low-density lipoprotein cholesterol (LDL) commonly called the “bad cholesterol.” This happens because a genetic mutation affects the way cholesterol is cleared/ recycled by the body. As a result, cholesterol builds up in the bloodstream and the walls of the arteries.

Cholesterol buildup in the artery wall is called plaque, hardening of the arteries, or atherosclerosis. This in turn can lead to premature health problems. Those include heart attacks and strokes in young adults and even children, specifically in HoFH.

Familial Hypercholesterolaemia (FH) presents in two forms:

  • Heterozygous Familial Hypercholesterolaemia (HeFH)
  • Homozygous Familial Hypercholesterolaemia (HoFH).
HoFH with Prof Wiegman
What is FH?
Atherosclerosis explained by Prof. Misère
Did you know?

Familial Hypercholesterolaemia can be spelt in British English as hypercholesterolaemia (with an “ae”) versus hypercholesterolemia in American English.  Regardless of the spelling, it is commonly referred to as FH in short, whereas the rare and severe form is referred to as HoFH.

What is Homozygous Familial Hypercholesterolemia (HoFH)?

HoFH is the rare and severe form of FH. It is estimated that HoFH affects 1 person in 300,000 people around the world[1]. HoFH happens when a child inherits two copies of an altered gene that causes FH, one copy from each parent. This is referred to as either compound heterozygous or homozygous FH (HoFH).

Individuals with HoFH typically have untreated LDL cholesterol levels ranging from ~400 mg/dL (~10 mmol/L) to ~1000 mg/dL (~26 mmol/L). So, it is roughly 4 to 10 times higher than the normal level.

If undiagnosed and untreated, HoFH can lead to cardiovascular complications, such as heart disease, including heart attacks and aortic valve disease, manifesting as early as childhood.

[1] 2023 Update on European Atherosclerosis Society Consensus Statement on Homozygous Familial Hypercholesterolaemia: new treatments and clinical guidance. Eur Heart J. 2023 Jul 1;44(25):2277-2291. doi: 10.1093/eurheartj/ehad197. PMID: 37130090; PMCID: PMC10314327.
Did you know?

There are 3 different cholesterol measurements taken: Total Cholesterol, HDL cholesterol (considered the “good cholesterol”) and LDL Cholesterol (referred to as “bad cholesterol).

In addition, there are different units used to reflect levels of cholesterol.

  • In many European countries and Canada, cholesterol levels are measured in millimoles per liter (mmol/L).
  • In the United States, cholesterol levels are measured in milligrams per deciliter (mg/dL).

Therefore, it is very important to know your numbers and units.

How is HoFH inherited? A family tree

HoFH is a genetic condition which occurs when a child inherits a copy of a mutated (changed) gene from each parent. In other words, HoFH follows an autosomal dominant pattern of inheritance, and it occurs when a variant is present on both alleles (copies) of a given gene.

There is another rare form of FH, called compound heterozygous FH. It only occurs if a person inherits two different types of gene alterations, one from each parent. These alterations may be different alterations in the same gene, or alterations in two of the three different genes associated with FH.

Did you know?

If both parents have FH, the probability having FH (HeFH or HoFH) changes and there is:

  • a one in two chance (50%) of inheriting one altered gene, which will cause HeFH
  • a one in four chance (25%) of inheriting two altered genes, which will cause HoFH

There is also a one in four chance (25%) of not inheriting any of the non-FH causing genes, meaning not having any form of FH.

Signs and Symptoms

Cholesterol Levels

Individuals with HoFH typically have very high levels of LDL cholesterol, exceeding 400 mg/dL (10 mmol/L) and raising up to 1000 mg/dL (26 mmol/L).

Family History

Since HoFH is an inherited condition, there is often a history of very high cholesterol levels and premature heart disease at both sides of the family. See the How is HoFH inherited? A family tree section above.


These are fatty deposits that accumulate under the skin, appearing as nodules or bumps. They can occur on various parts of the body, including the elbows, knees, hands, feet, and buttocks.


Yellowish cholesterol deposits can also form around the eyes, typically appearing as yellow patches or plaques on the eyelids.

Corneal Arcus

A whitish or grayish ring, starting at 6 o’clock, may appear around the cornea of the eye, known as corneal arcus. This is a common sign of high cholesterol levels.


The diagnosis of HoFH involves a multifaceted approach, including a simple blood test, a physical exam, and family history assessments (high cholesterol, premature cardiovascular disease (CVD) like heart attack or stroke, or premature death).

In addition, genetic testing is recommended in the process of diagnosis HoFH. Results of the genetic test will help understand the underlying causes, predict the severity of the condition and personalize the management plan/treatment for the best outcomes for the patient.

Verify with your local patient support group and lipid specialist if genetic testing is available and reimbursed in your country.

Importance of early diagnosis

It's crucial to recognize that HoFH is a significant and potentially life-threatening condition.

This disorder results in the early onset and progression of atherosclerosis, leading to premature heart disease, affecting both males and females, including children.

Therefore, upon receiving a diagnosis of HoFH for yourself or your child, one of the initial and urgent steps to undertake is to promptly seek specialized medical attention and to screen remaining relatives who might be unaware of the condition running in the family.

HoFH and genes – why knowing your genetic results is so important

This section is coming soon ......


HoFH can be effectively managed. Treatment of HoFH aims to lower LDL cholesterol levels and reduce the risk of cardiovascular events and should begin as soon as possible regardless of age.

A great deal of progress in HoFH treatment has been made in recent years and multiple effective treatments for HoFH exist today.  
Typically, a combination of treatments is necessary to reduce LDL cholesterol to recommended levels. Currently existing pharmacological options include:

DISCLAIMER: Note that images used below are for educational purposes only and are not promotional.


Statins inhibit cholesterol production in the liver. In HoFH, high doses of statins may be used to help lower LDL cholesterol levels.

Bempedoic Acid

A non-statin medication that reduces cholesterol levels in the bloodstream by inhibiting an enzyme present in the liver.


Ezetimibe is a medicine used to lower cholesterol in people who have high blood cholesterol. Ezetimibe works by reducing the amount of cholesterol your body absorbs from your intestines, in other words it inhibits the absorption of cholesterol from the intestines. It may be used in combination with statins to further lower LDL cholesterol levels.

Lipoprotein Apheresis

Lipoprotein apheresis is a procedure usually done every 2 weeks; it involves removing LDL cholesterol from the blood using a filtration system. 

PCSK9 Inhibitors

There are currently 3 types of PCSK9 inhibitors. Help improve the function of LDL receptors to remove LDL cholesterol from the bloodstream.

PCSK9 inhibitors are a relatively new class of medications designed to lower cholesterol levels in the blood. They work by inhibiting a protein called PCSK9, which is produced in the liver.

This is where knowing your specific genetic variant can play a significant role.

Repatha (Evolocumab)

Repatha is one of the approved PCSK9 inhibitors. It is a monoclonal antibody that binds to PCSK9, preventing it from breaking down LDL receptors on liver cells. By doing so, it increases the number of LDL receptors available to remove LDL cholesterol (often referred to as “bad cholesterol”) from the bloodstream. Clinical studies have shown that Repatha significantly lowers cholesterol levels and reduces the risk of cardiovascular diseases such as heart attacks and strokes.

Praluent (Alirocumab)

Praluent (Alirocumab): Praluent is another PCSK9 inhibitor. Like Repatha, it is a monoclonal antibody that targets PCSK9. By blocking PCSK9, Praluent increases the availability of LDL receptors, leading to decreased LDL cholesterol levels. Clinical trials have demonstrated its effectiveness in lowering cholesterol and reducing cardiovascular risk.

Inclisiran (Leqvio®)

Inclisiran is a newer PCSK9 inhibitor that has also received FDA approval. It works differently from Repatha and Praluent. Instead of being administered frequently, inclisiran is given as an injection every six months. It reduces PCSK9 production at the genetic level, resulting in increased LDL receptor expression and lowered cholesterol levels.

Lomitapide (Lojuxta / Juxtapid)

A microsomal triglyceride transfer protein (MTP) inhibitor, It can reduce LDL-C levels by ~50%. It is an oral daily pill, it is used alongside a low-fat diet and other lipid-lowering therapies specifically for adults diagnosed with HoFH. Unlike other therapies, Lomitapide does not work by trying to clear the high levels of cholesterol. It works by reducing the production and release of cholesterol from the liver and by reducing the absorption of cholesterol from the intestines following a meal. Specifically, Lomitapide is an oral, selective inhibitor of microsomal triglyceride transfer protein (MTP) a protein necessary for the proper assembly and secretion of cholesterol containing molecules in the liver and the intestines. Inhibition of MTP reduces the levels of cholesterol containing molecules including cholesterol, LDL-C and triglycerides in the blood. It is used alongside other lipid-lowering therapies for adults aged 18 and above diagnosed with HoFH.

IMPORTANT: if you're using Lomitapide, you should adhere to a low-fat diet instead of the typical healthy eating guidance.


A monoclonal antibody therapy that inhibits angiopoietin-like 3 (ANGPTL3)
It can reduce LDL-C levels by almost 50%. It is given monthly via infusion at the doctor's office. It is used alongside other lipid-lowering therapies for adults and children aged 5 and above diagnosed with HoFH.

Liver Transplant

In some rare circumstances, as the last resort, a surgical option can be considered.

Did you know?

Despite the recent research and development progress, not all of the above options may be available/reimbursed in every country. Additional therapies are in clinical trials and development. Those also include novel gene therapies.  For more specific information regarding treatment access in your country and or ongoing clinical trial, please contact your treating physician, your lipid specialist, your local patient support group.  

Worth knowing ...

A healthy lifestyle will not suffice if you have HoFH, but it is important to keep your overall physical and mental health in check. Also, a fat low diet is required to keep  lower cholesterol levels alongside some of the treatments.

Impact - Quality of life

Living with Homozygous Familial Hypercholesterolemia (HoFH) can have significant effects on mental wellbeing.

Emotional Impact:

  • Stress and Anxiety: Knowing you have a rare genetic condition like HoFH can cause stress and anxiety. The fear of heart attacks or other complications can be overwhelming. In our patient stories you will hear about how every pain can cause you to worry, waiting for something to happen,
  • Depression: Coping with chronic illness, especially one that affects heart health, can lead to depression. The burden of managing your cholesterol levels, medications and understanding when and how to take them, the side effects that impact movement, and lifestyle changes that also impact on your social life can take a toll.

Social and Emotional Isolation:

  • Stigma: Some with visible symptoms (such as cholesterol deposits under the eyes) may face stigma or feel self-conscious. In our patient stories you will hear of how growing up with these symptoms made going to school difficult. This can lead to social withdrawal.
  • Limited Activities: Due to the risk of heart disease, individuals with HoFH may avoid physical activities or social gatherings, impacting their quality of life. This often is caused through not wanting to show that you are unable to do things or keep others back.  Again in the stories you will find that patients do keep active but at a different pace and that can be difficult to explain when the condition is not visible and you look ‘fine’.

Family and Relationships:

  • Family Stress: Families of children with HoFH experience a lot of disruption and  immense stress. Imagine the emotional weight of having a child with such a severe condition and add to that the fact that often they feel the guilt of passing on faulty genes.  Giving so much attention to one sibling due to medical needs, treatment, etc can cause other family members to find it difficult to understand.
  • Cascade Screening: Sometimes, a child’s diagnosis of HoFH leads to cascade screening for the entire family. While this is essential for early detection, it can also cause anxiety for family members.  This is especially true when they do not understand the condition, treatments as well as the concern for some about what this would mean for their future prospects.

Coping Mechanisms:

  • Support Networks: Building a strong support network—friends, family, and healthcare professionals—can significantly improve mental wellbeing.
  • Education and Awareness: Understanding HoFH, its management, and available treatments empowers individuals and reduces anxiety.

Treatment and Hope:

  • Early Diagnosis: Early diagnosis allows for timely intervention and better outcomes. Knowing that effective treatments exist provides hope.
  • Treatment Success: Statins, non-statins, injectable medications, and lipoprotein apheresis can manage HoFH. Successful treatment can positively impact mental health. Our patient stories will highlight that you can live a full and fulfilled life with this condition.

Living with HoFH – stories told by the patients and their caregivers

Meet people from around the world affected with HoFH. The purpose of this video is to share real experiences of different people affected with the condition. Please note some people might find some of the stories very impactful.

Also watch our webinar - ‘Make it or Break it’ How you communicate about HoFH has an impact.

Living with HoFH
Make it or Break it
HoFH Latest Updates

Become an HoFH Ambassador

Become an ambassador and connect with other HoFH patients from around the world to exchange, learn, and support each other. FH Europe Foundation offers educational support to patients and caregivers who wish to become certified ambassadors to be actively involved in awareness raising and advocacy.

For more information contact elsie@fheurope.org

Find a Lipid Specialist

Visit https://findmylipidclinic.com to find a specialised lipid clinic close to you. And if you know of a clinic or a specialist, not listed on this website, do get in touch with the host to update it. This will improve the service and provide the much-needed help to other families affected with HoFH.

FH Europe Foundation partners with European Atherosclerosis Society FH Studies Collaboration, in short EAS FHSC, known as the global FH registry, to provide you with FindMyLipidClinic website.

Find a Lipid Specialist

Find a Support Group

FH Europe Foundation is an international network of patient organizations in over 30 countries supporting patients with Familial Hypercholesterolemia and other forms of inherited lipid conditions. Connect with your nearest patient group for more information and local support in your language. https://fhef.org/our-network/

Other support groups:

Resources on Demand

Over the years, together with international medical experts and HoFH patient Ambassadors, our community hosted a number of webinars and developed videos to help raise awareness and to educate.

Key Publications

This content has been developed by our Patient Ambassadors and reviewed by Prof. Albert Wiegman. Last review April 2024.