What is HoFH?

Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder that causes high levels of low-density lipoprotein (LDL) cholesterol in the blood. This condition is caused by mutations in genes that are involved in the metabolism of cholesterol, leading to a buildup of LDL cholesterol in the blood.

People with HoFH have very high levels of LDL cholesterol from birth, and if left untreated, this can lead to early heart disease and other complications. HoFH affects about 1 in 160,000 people worldwide.

Symptoms of HoFH The symptoms of HoFH can vary depending on the severity of the condition, but they often include:

• High levels of LDL cholesterol in the blood (typically greater than 500 mg/dL)
• Development of cholesterol deposits, or xanthomas, on the skin or tendons, especially around the knees, elbows, and buttocks
• Premature heart disease, including heart attacks, angina, and stroke
• Chest pain or discomfort
• Shortness of breath
• Palpitations
• Weakness or fatigue
• Swelling in the legs or ankles
• Yellowish discoloration of the skin or eyes (jaundice)

Diagnosis of HoFH HoFH is typically diagnosed through blood tests that measure the levels of LDL cholesterol and other lipids in the blood. A genetic test can also confirm the diagnosis by identifying mutations in genes that are associated with HoFH.

It is important for individuals with a family history of HoFH or high cholesterol levels to undergo screening tests for this condition, as early diagnosis and treatment can help prevent complications.

Treatment of HoFH HoFH is a serious condition that requires lifelong management. The primary treatment goal is to lower LDL cholesterol levels to reduce the risk of cardiovascular complications.

Treatment options for HoFH include lifestyle changes, medications, and in some cases, surgery. Some lifestyle changes that can help manage HoFH include:

• Eating a heart-healthy diet that is low in saturated and trans fats
• Engaging in regular physical activity
• Maintaining a healthy weight
• Quitting smoking

Medications used to treat HoFH include:

• Statins, which block the production of cholesterol in the liver
• Ezetimibe, which reduces the absorption of cholesterol in the intestines
• PCSK9 inhibitors, which target a protein that helps regulate LDL cholesterol levels
• Bile acid sequestrants, which bind to bile acids in the intestines and help eliminate them from the body

In some cases, surgery may be necessary to remove cholesterol deposits from the skin or tendons.

In addition to medication, some people with HoFH may also benefit from apheresis, a process that involves removing LDL cholesterol from the blood using a machine that functions similar to dialysis. This treatment is typically reserved for people with severe HoFH who do not respond to other treatments.

Prevention of HoFH HoFH is a genetic condition, which means that it cannot be prevented. However, genetic testing can identify individuals who are at risk for HoFH and allow for early diagnosis and treatment. Additionally, lifestyle changes such as maintaining a healthy diet and engaging in regular physical activity can help reduce the risk of cardiovascular complications associated with HoFH.

In summary, HoFH is a rare genetic disorder that causes high levels of LDL cholesterol in the blood, leading to a buildup of cholesterol deposits and an increased risk of heart disease and other complications. Treatment involves lifelong management through lifestyle changes, medications, and in some cases, surgery or apheresis. Early diagnosis and treatment can help prevent complications, and genetic testing can identify individuals who are at risk for HoFH.