What is homozygous familial hypercholesterolemia?

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The main sign of HoFH is extremely high blood cholesterol.

Blood tests may show low-density lipoprotein (LDL) cholesterol levels of 400 to 1,000 milligrams per deciliter (mg/dL), around 4 to 10 times higher than the typical range.

A person with raised LDL cholesterol may also experience the following symptoms:

• xanthomas, or a yellow tint to the skin, affecting the hands, elbows, knees, or buttocks
• corneal arcus, or a gray, yellow, or white ring on the surface of the eye
• increased thickness of, or nodules on, the Achilles tendon

Spotting these symptoms early in life is essential. Without treatment, children as young as 2 to 3 years can develop heart disease due to HoFH.

HoFH can lead to heart attacks in children as young as 7 years.

Learn more about FH.

HoFH is a genetic condition. It occurs due to mutations in certain genes that control how the body processes and removes cholesterol from the bloodstream.

Genes involved

The specific genes that develop mutations in those with HoFH include:

• LDLR
• APOB
• PCSK9

Biological parents can pass genes with these mutations onto their children. If only one parent passes on the gene, the condition is known as heterozygous familial hypercholesterolemia (HeFH). This is less severe and more common than HoFH.

If both parents pass on mutations in these genes, HoFH can develop.

Risk factors

Some groups are more likely to acquire HoFH than others, though anyone can develop it if they have two parents with the mutated gene. These groups include:

• people of Ashkenazi Jewish heritage from Lithuania
• Lebanese Christian people
• French Canadian people
• Afrikaner people in South Africa

Learn more about genetics and high cholesterol.

Doctors typically diagnose HoFH by performing a physical examination, taking a full personal and family medical history, and ordering blood tests.

They may also perform genetic testing to determine the exact mutation a person has inherited. If family members are aware of a specific FH mutation, the doctor will request tests for this mutation.

Genetic testing identifies the mutation in 60% to 80% of people with FH. If a doctor diagnoses HoFH in an individual whose parents were not aware of having FH, they will likely carry out cascade screening, which means extending testing to other biological relatives with a high risk of developing the condition.

Several medications can help bring down blood cholesterol levels and reduce the risk of severe heart problems in people with HoFH.

Medications

HoFH medications include:

• Statins: Statins are oral medications that reduce the amount of LDL cholesterol the liver makes and increase how much the body removes from the bloodstream.
• Ezetimibe: This daily oral pill reduces the amount of LDL cholesterol the gut absorbs from food and increases the amount the body takes from the blood.
• PCSK9 inhibitors: PCSK9 inhibitors are injectable medications that switch off a protein called PCSK9, which would otherwise attack receptors in the body that remove LDL cholesterol from the blood. People receive 1 to 2 injections per month.
• Bempedoic acid: This daily oral pill blocks an enzyme called ATP citrate lyase in the liver, reducing cholesterol levels.
• Lomitapide: Lomitapide is a daily oral pill that can reduce LDL cholesterol by 40% to 50% by reducing how much the liver makes and bringing down the amount the gut absorbs. Only adults with HoFH can use it.
• Evinacumab: This monoclonal antibody therapy blocks a protein called ANGPTL3 and reduces LDL cholesterol by 45% to 50%. Children over 12 years of age and adults with HoFH can receive this monthly infusion in a doctor’s office.

Lipoprotein apheresis

If medications are ineffective, lipoprotein apheresis can help reduce LDL cholesterol by 20% to 40%.

It involves removing the blood from the body via an infusion so that a medical team can remove the lipids (blood fats), including LDL cholesterol. They then return the blood to the body.

Liver transplant

A liver transplant may return cholesterol to normal levels. In this procedure, a surgeon removes a person’s liver and replaces it with a donor liver. However, doctors rarely recommend liver transplants for HoFH.

Learn more about treatments for high cholesterol in young adults.

Do statins work for homozygous familial hypercholesterolemia?

Statins are the first-line treatment for HoFH.

They might reduce LDL cholesterol by 35% to 55% and lower the risk of heart disease by 22% with every 40 mg/dL reduction in LDL cholesterol. They are also safe for children.

Statins for HoFH include:

• fluvastatin (Lescol, Lescol XL)
• lovastatin (Mevacor, Altoprev)
• pitavastatin (Livalo, Zypitamag)
• pravastatin (Pravachol)
• simvastatin (Zocor)

High intensity statins, including atorvastatin (Lipitor) and rosuvastatin (Crestor), are available for people with very high LDL cholesterol levels.

Learn more about statins for cholesterol management.

According to the American Journal of Managed Care, people with HoFH have a life expectancy of fewer than 30 years.

However, a 2018 analysis found that reducing LDL cholesterol with medications can increase the time until a person’s first cardiac event by an average of 8.3 years and their life expectancy by an average of 14.5 years.

The earlier a person with HoFH starts taking medications, the more they may be able to extend their life expectancy.

HoFH is rare, affecting 1 in 300,000 people in the United States.

According to the Centers for Disease Control and Prevention (CDC), each parent with FH has a 50% chance of passing on the genes linked to HoFH.

Several important differences separate HoFH and HeFH. The table below illustrates these:

Homozygous familial hypercholesterolemia (HoFH) is a rare inherited condition that causes extremely high levels of low-density lipoprotein (LDL) cholesterol. People with HoFH inherit one mutated gene from each biological parent, which can increase a person’s risk of heart attacks, even during childhood.

Without treatment, a person with HoFH has a life expectancy of around 30 years. However, various medications are available to reduce cholesterol levels.

If cholesterol levels do not respond to medications, a procedure called lipoprotein apheresis can remove cholesterol from the blood.