What are the symptoms of homozygous familial hypercholesterolemia?

Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder characterized by very high levels of low-density lipoprotein (LDL) cholesterol from birth, which can lead to early and severe cardiovascular disease. Symptoms of HoFH can include:

1. High cholesterol levels: HoFH is characterized by extremely high levels of LDL cholesterol, often above 500 mg/dL (milligrams per deciliter) in adults and even higher in children.
2. Early onset of cardiovascular disease: Individuals with HoFH are at a very high risk of developing cardiovascular disease, including heart attacks and strokes, often at a young age.
3. Xanthomas: These are deposits of cholesterol that can form under the skin, typically around the eyes (xanthelasma) or on the tendons, such as the Achilles tendon.
4. Corneal arcus: A white or gray ring around the cornea of the eye, which is caused by cholesterol deposits.
5. Heart disease symptoms: These can include chest pain (angina), shortness of breath, and other symptoms of heart disease.
6. Premature heart disease: Individuals with HoFH often develop heart disease in their 20s or 30s, much earlier than the general population.

It’s important to note that HoFH is a severe form of hypercholesterolemia and requires early diagnosis and aggressive treatment to prevent cardiovascular complications. If you or someone you know has a family history of early heart disease or has symptoms of HoFH, it’s important to consult with a healthcare provider for proper evaluation and management.

What are the causes of homozygous familial hypercholesterolemia?

Homozygous familial hypercholesterolemia (HoFH) is caused by mutations in both copies of the gene that encodes the low-density lipoprotein receptor (LDLR), which is responsible for removing LDL cholesterol from the bloodstream. As a result of these mutations, the LDLR is either absent or defective, leading to extremely high levels of LDL cholesterol in the blood. HoFH is inherited in an autosomal recessive pattern, which means that an individual must inherit two copies of the mutated gene (one from each parent) to develop the condition.

What is the treatment for homozygous familial hypercholesterolemia?

The treatment for homozygous familial hypercholesterolemia (HoFH) is aimed at reducing LDL cholesterol levels as much as possible to lower the risk of cardiovascular complications. Since HoFH is a severe form of hypercholesterolemia that does not respond well to standard cholesterol-lowering medications, treatment usually involves a combination of approaches, including:

1. Lifestyle changes: A heart-healthy diet low in saturated fats and cholesterol, regular physical activity, and avoiding tobacco smoke can help manage cholesterol levels and reduce the risk of cardiovascular disease.
2. Cholesterol-lowering medications: In addition to standard cholesterol-lowering medications such as statins, individuals with HoFH may require other medications that target cholesterol, such as ezetimibe, bile acid sequestrants, and PCSK9 inhibitors. These medications can help lower LDL cholesterol levels, but they may not be as effective in HoFH as in other forms of hypercholesterolemia.
3. LDL apheresis: This is a procedure similar to dialysis that filters LDL cholesterol out of the blood. LDL apheresis can rapidly lower LDL cholesterol levels and is often used in individuals with HoFH who do not respond well to medications alone. However, it is a costly and time-consuming procedure that needs to be repeated regularly.
4. Liver transplant: In some cases, a liver transplant may be considered for individuals with HoFH. Since the liver is the primary source of LDL receptors, a liver transplant can provide a new source of functional LDL receptors, which can help lower LDL cholesterol levels.
5. Clinical trials: There are ongoing clinical trials investigating new treatments for HoFH, including gene therapy and novel cholesterol-lowering medications. Participation in these trials may offer new treatment options for individuals with HoFH.

Since HoFH is a rare and serious condition, management should be guided by healthcare professionals with expertise in lipid disorders. Treatment should be individualized based on the severity of the condition, the response to treatment, and other factors specific to each patient.