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Friday, March 28
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Understanding Homozygous Familial Hypercholesterolaemia (HoFH): A Patient Guide

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Understanding Homozygous Familial Hypercholesterolaemia (HoFH): A Patient Guide

Homozygous familial hypercholesterolaemia (HoFH) is a rare genetic condition that causes extremely high levels of low-density lipoprotein (LDL) cholesterol (often called “bad cholesterol”) from birth. This guide explains the condition, its causes, symptoms, treatments, and how to manage living with it.

What is Homozygous Familial Hypercholesterolaemia?

HoFH is a severe form of familial hypercholesterolaemia (FH), a genetic condition that affects how your body processes cholesterol. In HoFH, individuals inherit faulty copies of the LDLR gene (or related genes) from both parents. This results in very high LDL cholesterol levels in the blood, which can lead to the early buildup of fatty deposits in arteries (atherosclerosis). Without treatment, HoFH significantly increases the risk of heart disease and stroke at an early age.

Background on HoFH

  • History: FH was first described in the 1930s, and HoFH was later recognised as a more severe form of this condition.
  • Global Impact: While rare, HoFH has a significant impact due to its association with early cardiovascular disease. Early diagnosis and treatment are critical for improving outcomes.

Causes, Incidence, and Prevalence

Causes

HoFH is caused by mutations in genes involved in removing LDL cholesterol from the blood. These genes include:

  • LDLR: Responsible for making LDL receptors that remove LDL cholesterol from the blood.
  • APOB: Provides instructions for a protein that binds to LDL receptors.
  • PCSK9: Regulates the number of LDL receptors available on cells.

In HoFH, individuals inherit two faulty copies of these genes—one from each parent—which severely limits or eliminates the body’s ability to clear LDL cholesterol.

Incidence and Prevalence

  • Incidence: HoFH is estimated to occur in 1 in 300,000 to 1 in 1 million people worldwide, making it an ultra-rare condition.
  • Prevalence: Due to its rarity, exact prevalence rates vary by region but may be higher in populations with higher rates of consanguinity (marriage between close relatives).

Who is Affected?

  1. Age of Onset: Symptoms begin at birth due to extremely high cholesterol levels.
  2. Gender: Both males and females are equally affected.
  3. Ethnicity: HoFH occurs across all ethnic groups but may be more common in certain populations such as Afrikaners (South Africa), French Canadians, Lebanese, and Ashkenazi Jews due to higher rates of specific genetic mutations.

Geographic Distribution

HoFH has been reported worldwide but is more prevalent in populations with higher rates of familial hypercholesterolaemia due to genetic factors.

How Does HoFH Impact You?

Symptoms

The symptoms and complications of HoFH result from extremely high LDL cholesterol levels and may include:

  • Fatty deposits (xanthomas) on the skin or tendons, often visible by childhood.
  • Fatty deposits around the eyes (xanthelasmas).
  • Early signs of heart disease or chest pain (angina), sometimes as early as childhood or adolescence.
  • Narrowing or blockages in arteries due to atherosclerosis.

Without treatment, HoFH can lead to life-threatening complications such as heart attacks or strokes at a young age.

Living With HoFH

Living with HoFH requires lifelong management of cholesterol levels through medications, lifestyle changes, and regular monitoring by healthcare professionals.

Expected Life Expectancy

Without treatment, individuals with HoFH often develop cardiovascular disease before age 20 and may not survive beyond their 30s. However, advances in treatments have significantly improved life expectancy for many patients.

Managing and Treating Homozygous Familial Hypercholesterolaemia

Available Treatments

Treatment for HoFH focuses on aggressively lowering LDL cholesterol levels to reduce the risk of cardiovascular complications:

  1. Medications:
    1. Statins: High-intensity statins like atorvastatin or rosuvastatin are used to lower LDL cholesterol production.
    2. Ezetimibe: Reduces cholesterol absorption from food.
    3. PCSK9 Inhibitors: Injectable medications like alirocumab or evolocumab enhance the removal of LDL cholesterol from the blood.
    4. Bempedoic Acid: A newer oral medication that lowers LDL cholesterol by targeting a specific enzyme involved in its production.
    5. Lomitapide: Reduces the production of lipoproteins that carry cholesterol.
    6. Mipomersen: Targets specific RNA molecules to reduce LDL cholesterol production.
  1. Advanced Therapies:
    1. Lipoprotein Apheresis: A procedure similar to dialysis that removes LDL cholesterol directly from the blood; often required weekly or biweekly.
    2. Gene Therapy: Experimental treatments aim to correct genetic mutations responsible for HoFH.
  1. Lifestyle Changes:
    1. Follow a heart-healthy diet low in saturated fats and trans fats while rich in fruits, vegetables, whole grains, and lean proteins.
    2. Engage in regular physical activity tailored to your abilities.
    3. Avoid smoking and limit alcohol consumption.

Ongoing Clinical Research

Research into HoFH continues to explore new therapies aimed at improving outcomes for patients:

  • Gene Editing Techniques: Technologies like CRISPR-Cas9 are being studied for their potential to correct genetic mutations permanently.
  • RNA-Based Therapies: Drugs targeting specific pathways involved in cholesterol metabolism are under investigation.
  • Longer-Acting PCSK9 Inhibitors: Trials are underway for medications that require less frequent dosing while maintaining effectiveness.
  • For information on clinical trials related to HoFH, visit gov.

Support Groups and Resources

If you have been diagnosed with HoFH or have a family history of this condition, connecting with support groups can provide valuable information and emotional support:

  1. Heart UK – The Cholesterol Charity (org.uk)– Offers resources specifically for individuals struggling with high cholesterol conditions like HoFH.
  2. Familial Hypercholesterolemia Foundation (FH Foundation) (org)– Focuses on education and advocacy for people living with inherited high cholesterol conditions.
  3. British Heart Foundation (BHF) (org.uk)– Provides general support for managing cardiovascular health.
  4. European Atherosclerosis Society (EAS) (eas-society.org)– Offers educational resources on lipid disorders like HoFH.

    Remember:

    This information is intended for general knowledge and educational purposes only and does not constitute medical advice. It is essential to consult with a qualified healthcare professional for any health concerns or before making any decisions related to your health or treatment.