Familial Hypercholesterolemia
Disease Details
Family Health Simplified
- Description
- Familial hypercholesterolemia is a genetic disorder characterized by high cholesterol levels, specifically very high levels of low-density lipoprotein (LDL), starting at birth and resulting in an increased risk of heart disease.
- Type
- Familial hypercholesterolemia is primarily transmitted in an autosomal dominant manner. This means that an individual needs only one copy of the mutated gene from one parent to inherit the condition.
- Signs And Symptoms
-
Signs and symptoms of familial hypercholesterolemia (FH) include:
1. Elevated levels of low-density lipoprotein (LDL) cholesterol from a young age.
2. Xanthomas, which are fatty deposits often seen on tendons and around the eyes.
3. Corneal arcus, a gray or white arc visible around the cornea of the eye.
4. Early onset of cardiovascular disease, including heart attacks and angina.
5. A family history of high cholesterol or early heart disease. - Prognosis
- Familial hypercholesterolemia is a genetic disorder characterized by high cholesterol levels, specifically low-density lipoprotein (LDL) cholesterol, which can lead to premature cardiovascular disease. The prognosis for individuals with familial hypercholesterolemia largely depends on early diagnosis and effective management. With appropriate lifestyle changes and medications such as statins, individuals can significantly reduce their risk of heart disease and improve their overall prognosis. However, without proper treatment, there is a significantly increased risk of early heart attacks and other cardiovascular events. Early detection and ongoing management are crucial for improving outcomes.
- Onset
- Familial hypercholesterolemia typically has an early onset, often visible in childhood or adolescence. Elevated cholesterol levels can be detected from a very young age.
- Prevalence
- The prevalence of familial hypercholesterolemia varies by population, but it is estimated to occur in approximately 1 in 250 individuals globally. In certain populations, the prevalence can be higher due to genetic factors.
- Epidemiology
- Familial hypercholesterolemia is a common inherited disorder. It affects approximately 1 in 250 individuals globally. The condition is characterized by high levels of low-density lipoprotein (LDL) cholesterol, which significantly increases the risk of cardiovascular disease at an early age.
- Intractability
- Familial hypercholesterolemia (FH) is not considered intractable, meaning it can be managed and treated, although it cannot be cured. Management typically includes lifestyle changes, such as diet and exercise, and medications like statins, ezetimibe, or PCSK9 inhibitors to lower cholesterol levels. In some severe cases, LDL apheresis, a procedure to remove LDL cholesterol from the blood, may be necessary. Early diagnosis and aggressive treatment are crucial to reducing the risk of cardiovascular complications associated with FH.
- Disease Severity
- Familial hypercholesterolemia is a serious genetic disorder characterized by high levels of low-density lipoprotein (LDL) cholesterol, which significantly increases the risk of cardiovascular disease, including heart attacks and strokes, at an early age. The severity can vary, with homozygous individuals (those with two copies of the mutated gene) typically experiencing more severe symptoms and complications compared to heterozygous individuals (those with one copy of the mutated gene). If untreated, this condition can lead to early-onset cardiovascular events and reduced life expectancy.
- Healthcare Professionals
- Disease Ontology ID - DOID:13810
- Pathophysiology
-
Familial hypercholesterolemia (FH) is a genetic disorder characterized by high cholesterol levels, specifically elevated low-density lipoprotein (LDL) cholesterol, in the blood.
Pathophysiology:
- FH is primarily caused by mutations in the LDL receptor (LDLR) gene, which impairs the normal function of the LDL receptors on liver cells that remove LDL cholesterol from the blood.
- Mutations may also occur in the apolipoprotein B (APOB) gene, which provides instructions for making a protein that helps LDL receptors recognize and bind to LDL cholesterol.
- Additionally, mutations in the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene can increase the degradation of LDL receptors, exacerbating high cholesterol levels.
- The defective or insufficient number of LDL receptors results in decreased clearance of LDL cholesterol, leading to its accumulation in the bloodstream.
- This condition significantly increases the risk of atherosclerosis, which can lead to coronary artery disease and other cardiovascular complications at an early age. - Carrier Status
-
In the context of familial hypercholesterolemia, "carrier status" typically refers to whether an individual carries one or two copies of the mutated gene associated with the condition:
1. **Heterozygous Familial Hypercholesterolemia (HeFH)**: An individual carries one copy of the mutated gene. This form is more common and presents with elevated cholesterol levels and an increased risk of cardiovascular disease, typically manifesting in adulthood.
2. **Homozygous Familial Hypercholesterolemia (HoFH)**: An individual carries two copies of the mutated gene, one from each parent. This form is rarer and more severe, often leading to extremely high cholesterol levels and early onset cardiovascular complications, sometimes in childhood.
Nan (Not a Number) is not applicable here as it doesn't provide relevant information about the carrier status. - Mechanism
-
Familial hypercholesterolemia (FH) is a genetic disorder characterized by high levels of low-density lipoprotein cholesterol (LDL-C) in the blood.
**Mechanism:**
FH typically results from mutations in genes involved in the metabolism of LDL-C, primarily the LDL receptor (LDLR) gene. Mutations can also occur in the apolipoprotein B (APOB) gene and the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene. These mutations disrupt the normal clearance of LDL-C from the bloodstream, leading to elevated cholesterol levels and increased risk of cardiovascular diseases.
**Molecular Mechanisms:**
1. **LDLR Gene Mutations:**
- LDLR is responsible for the uptake of LDL particles from the bloodstream into cells.
- Mutations can lead to a decrease in the number or function of LDL receptors, resulting in impaired clearance of LDL-C and its accumulation in the blood.
2. **APOB Gene Mutations:**
- APOB is the primary protein component of LDL particles and is essential for the binding of LDL to its receptor.
- Mutations can reduce the affinity of LDL for the LDL receptor, hindering its clearance and causing elevated LDL-C levels.
3. **PCSK9 Gene Mutations:**
- PCSK9 regulates the degradation of LDL receptors.
- Mutations leading to increased PCSK9 activity result in reduced LDL receptor levels on cell surfaces, decreasing the uptake of LDL-C from the bloodstream.
These genetic mutations collectively contribute to the high cholesterol levels observed in FH, necessitating early intervention and management to reduce cardiovascular risks. - Treatment
-
Treatment for familial hypercholesterolemia typically includes:
1. **Medications:**
- **Statins:** Help lower cholesterol levels by inhibiting the enzyme HMG-CoA reductase.
- **Ezetimibe:** Reduces the amount of cholesterol absorbed by the intestines.
- **PCSK9 inhibitors:** Increase the liver's ability to remove LDL cholesterol from the blood.
- **Bile acid sequestrants:** Bind bile acids in the intestine, forcing the body to use excess cholesterol to make more bile acids.
- **Lomitapide:** Inhibits microsomal triglyceride transfer protein to lower LDL cholesterol.
- **Mipomersen:** An oligonucleotide inhibitor of apolipoprotein B synthesis.
2. **Lifestyle Changes:**
- Diet: Low in saturated fats and cholesterol.
- Regular physical activity.
- Avoid smoking, and limit alcohol intake.
- Maintain a healthy weight.
3. **Advanced Therapies:**
- **LDL apheresis:** A procedure to physically remove LDL cholesterol from the blood, used in severe cases.
- **Liver transplant:** Rarely, in extremely severe cases.
Regular monitoring by a healthcare provider is essential to track cholesterol levels and adjust treatment as needed. - Compassionate Use Treatment
-
For familial hypercholesterolemia, compassionate use treatments and off-label or experimental treatments may be considered in severe or refractory cases. Some potential options include:
1. **PCSK9 Inhibitors**: Although already approved for use, these can sometimes be accessed under compassionate use for patients who cannot achieve target LDL-C levels with existing therapies.
2. **Lomitapide**: This microsomal triglyceride transfer protein (MTP) inhibitor, primarily used in homozygous familial hypercholesterolemia, may sometimes be used off-label or through compassionate use in severe cases where other treatments are insufficient.
3. **Evinacumab**: An angiopoietin-like 3 (ANGPTL3) inhibitor is under investigation but may be available through expanded access or clinical trials.
4. **Lipoprotein Apheresis**: This is a process similar to dialysis that can rapidly reduce LDL-C levels and might be considered an off-label or last-resort treatment in extreme cases.
5. **Gene Therapy**: Experimental gene therapies are in development and might be available through clinical trials.
Patients should consult with specialists to evaluate these options based on individual clinical circumstances. - Lifestyle Recommendations
-
### Lifestyle Recommendations for Familial Hypercholesterolemia (FH)
1. **Dietary Changes**:
- **Reduce Saturated Fats**: Limit intake of red meat, full-fat dairy products, and processed foods.
- **Increase Fiber Intake**: Consume more fruits, vegetables, whole grains, and legumes.
- **Healthy Fats**: Opt for monounsaturated and polyunsaturated fats, such as those found in olive oil, avocado, nuts, and fatty fish.
- **Reduce Cholesterol Intake**: Limit high-cholesterol foods like organ meats and shellfish.
2. **Physical Activity**:
- **Regular Exercise**: Engage in at least 150 minutes of moderate-intensity aerobic activity or 75 minutes of vigorous-intensity activity per week.
- **Strength Training**: Include muscle-strengthening activities on two or more days per week.
3. **Weight Management**:
- **Achieve/maintain healthy weight**: Follow a balanced diet and exercise regularly to maintain a healthy body weight.
4. **Avoid Tobacco**:
- **Quit Smoking**: Avoid smoking and exposure to secondhand smoke to improve overall cardiovascular health.
5. **Limit Alcohol**:
- **Moderation is Key**: If you drink alcohol, do so in moderation, defined as up to one drink per day for women and up to two drinks per day for men.
6. **Regular Medical Check-ups**:
- **Routine Monitoring**: Regularly check cholesterol levels and follow medical advice for managing FH.
7. **Adhere to Medication**:
- **Follow Prescriptions**: Take any prescribed medications, such as statins, as directed by your healthcare provider.
Implementing these lifestyle changes can help manage cholesterol levels and reduce the risk of cardiovascular complications associated with familial hypercholesterolemia. - Medication
- Medications for familial hypercholesterolemia typically include statins (e.g., atorvastatin, simvastatin) to lower LDL cholesterol levels. Other options may include ezetimibe, bile acid sequestrants, PCSK9 inhibitors (e.g., alirocumab, evolocumab), and in some cases, lomitapide or mipomersen. Combination therapy is often used for more effective management.
- Repurposable Drugs
- There are currently no widely recognized or approved repurposable drugs specifically for familial hypercholesterolemia. This condition, characterized by high cholesterol levels due to genetic mutations, traditionally requires treatments such as statins, ezetimibe, PCSK9 inhibitors, and lifestyle changes. Research is ongoing, and new therapeutic options may emerge as our understanding progresses.
- Metabolites
-
Familial hypercholesterolemia (FH) is characterized by elevated levels of low-density lipoprotein cholesterol (LDL-C). Key metabolites associated with FH include:
- **LDL cholesterol (LDL-C)**: Elevated levels are a hallmark of FH.
- **Total cholesterol**: Increased levels due to high LDL-C.
- **Triglycerides**: Levels may be normal or slightly elevated.
- **Lipoprotein(a)**: Often increased in individuals with FH, contributing to cardiovascular risk.
Routine genetic testing and lipid profile analyses help in diagnosing and managing the condition. - Nutraceuticals
- For familial hypercholesterolemia (FH), nutraceuticals such as plant sterols and stanols, soluble fiber, omega-3 fatty acids, and red yeast rice may be recommended to help manage cholesterol levels. These supplements can support traditional treatments but should not replace prescribed medications. Always consult with a healthcare provider before starting any nutraceutical regimen for FH.
- Peptides
- Familial hypercholesterolemia (FH) is not directly treated using peptides or nanotechnology as standard practices. However, ongoing research explores the use of peptides and nanotechnology-based interventions for lipid disorders, potentially including FH. Current treatments primarily involve lifestyle modifications, statins, and other lipid-lowering medications to manage cholesterol levels.