familial hypercholesterolemia

Familial Hypercholesterolemia (FH): A Genetic Disorder

Familial hypercholesterolemia, also known as FH, is a genetic disorder that affects the way the body recycles low-density lipoprotein (LDL), or "bad" cholesterol. This inherited condition causes high levels of LDL cholesterol to build up in the bloodstream, leading to early heart attacks and other cardiovascular problems.

Key Characteristics:

• Inherited: FH is passed down from parents to children through genes.
• High Cholesterol Levels: People with FH have extremely high levels of "bad" cholesterol, even in childhood.
• Early Heart Attacks: If left untreated, FH can lead to early heart attacks and other cardiovascular problems.
• Increased Risk: Individuals with FH are at a higher risk of developing heart disease at a younger age than usual.

Causes and Symptoms:

• Genetic Defect: FH is caused by a genetic defect that affects the way the body recycles LDL cholesterol.
• High Cholesterol Levels: People with FH have high levels of LDL cholesterol, which can lead to early heart attacks and other cardiovascular problems.
• Early Symptoms: Early symptoms may include high cholesterol levels, early heart attacks, and other cardiovascular problems.

References:

• [1] Familial hypercholesterolemia (FH) is an inherited defect in how the body recycles LDL, or “bad” cholesterol. People with FH are born with high ...
• [2] This inherited condition can cause extremely high levels of "bad" cholesterol, even in childhood, and can lead to early heart attacks and ...
• [3] Familial hypercholesterolemia (FH) is an inherited condition that causes high blood levels of low-density lipoprotein (LDL) cholesterol.
• [4] Familial hypercholesterolemia (FH) is an inherited condition that increases your risk of heart disease at a younger age than usual.
• [5] Familial hypercholesterolemia is an inherited genetic condition that is present from birth (congenital) and causes high levels of low density lipoprotein ...
• [6] Familial hypercholesterolemia (FH) is a genetic disorder that causes abnormal buildup of LDL, or "bad" cholesterol. Learn about symptoms and treatment.
• [7] Nov 7, 2024 — Familial hypercholesterolemia (FH) is a common life-threatening genetic condition that causes high cholesterol. If left untreated, FH leads ...
• [8] by Z Vaezi · 2022 · Cited by 17 — Familial hypercholesterolemia is a group of inherited genetic defects that lead to the severe elevation of serum cholesterol concentrations.
• [9] Mar 13, 2024 — Familial hypercholesterolemia (FH) is an autosomal dominant disorder that causes severe elevations in total cholesterol and low-density ...
• [10] Result: noun | congenital disorder characterized by high levels of cholesterol and early development of atherosclerosis

Familial hypercholesterolemia (FH) is a genetic disorder that causes an abnormal buildup of low-density lipoprotein (LDL), also known as "bad" cholesterol, in the body. This condition can lead to various signs and symptoms, which are often related to the cardiovascular system.

Common Signs and Symptoms:

• Bumps or lumps around the knees, knuckles, or elbows, known as xanthomas [1]
• Swollen or painful Achilles tendon (the tendon at the back of your heel) [1]
• Chest pain (angina) [4]
• Coronary artery disease [4]
• Fatty deposits around the body (xanthomas) [4]
• Cholesterol deposits on the eyelid (xanthelasma) [5]

Other Possible Symptoms:

• Nodules or raised bumps on your skin or tendons, also known as xanthomas [5]
• Bumps on your upper or lower eyelids, called xanthelasma [5]
• White, blueish, or yellowish patches on the skin, which can be a sign of cholesterol buildup [5]

Early Detection and Treatment:

It's essential to detect familial hypercholesterolemia early, as it can lead to severe cardiovascular complications if left untreated. High levels of LDL cholesterol in childhood can indicate this condition, and early treatment with statins or other medications can help manage the symptoms and prevent long-term damage.

References:

[1] Signs and symptoms · Bumps or lumps around your knees, knuckles, or elbows · Swollen or painful Achilles tendon (the tendon at the back of your ... [Context 1]

[4] Symptoms · Chest pain (angina) · Coronary artery disease · Fatty deposits around the body (xanthomas) · Cholesterol deposits on the eyelid (xanthelasmas) · Sores on ... [Context 4]

[5] Mar 9, 2022 — Nodules or raised bumps on your skin or tendons (called xanthomas); Bumps on your upper or lower eyelids (called xanthelasma); White, blueish or ... [Context 5]

Diagnostic Tests for Familial Hypercholesterolemia (FH)

Familial hypercholesterolemia, a genetic disorder characterized by high cholesterol levels, can be diagnosed through various tests. Here are the key diagnostic tests for FH:

• Lipid Test: A simple blood test to measure the amount of LDL (bad) cholesterol in the blood is a crucial step in diagnosing FH [4][5]. This test measures the level of LDL cholesterol and helps identify individuals with high levels, which is a hallmark of FH.
• Genetic Testing: Genetic testing for inherited genetic changes known to cause FH can confirm the diagnosis. The most commonly affected genes are LDLR, APOB, and PCSK9 [1].
• Family History: A detailed family history is essential in diagnosing FH. Doctors will ask about the patient's siblings, parents, and other relatives with high cholesterol levels or a history of heart disease [2].
• Physical Exam: A physical exam can also help diagnose FH. Tendon xanthomas (deposits of cholesterol under the skin) are a characteristic feature of heterozygous FH and can be detected during a physical examination [8].

Additional Diagnostic Tools

• The Simon Broom criteria, Med Ped Criteria, and the FH Dutch Lipid Clinic Network criteria are three accepted resources for diagnosing FH [10].
• A probable diagnosis of heterozygous FH can be made if the LDLc level is greater than 330 mg/dL or if tendon xanthomas are present in a patient with a family history of high cholesterol levels [8].

References

[1] May 15, 2024 — Genetic testing for familial hypercholesterolemia (FH) looks for inherited genetic changes known to cause FH...

[2] A detailed family history is an important key to diagnosing familial hypercholesterolemia.

[3] The Familial Hypercholesterolemia Single-Site test (test code 94878) is available for targeted testing, when 1 or 2 familial pathogenic variants are known.

[4] Nov 7, 2024 — FH is typically diagnosed clinically with a lipid test measuring the amount of LDL cholesterol in the blood...

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Treatment Options for Familial Hypercholesterolemia (FH)

Familial hypercholesterolemia, a genetic disorder characterized by high levels of low-density lipoprotein (LDL) cholesterol, can be managed with various drug treatments. The primary goal is to lower LDL cholesterol levels and prevent cardiovascular complications.

1. Statins

Statins are the most commonly prescribed medications for FH patients. They work by inhibiting the enzyme HMG-CoA reductase, which plays a key role in cholesterol production in the liver. Statin therapy can be initiated at an early age, even in children diagnosed with FH [2].

2. PCSK9 Inhibitors

PCSK9 inhibitors, such as alirocumab (Praluent) and evolocumab (Repatha), are newer drugs that help the liver absorb more LDL cholesterol, thereby lowering its levels in the blood [1]. These medications can be used alone or in combination with other lipid-lowering therapies.

3. Combination Therapy

Combination therapy is frequently employed to achieve optimal LDL cholesterol reduction. This may involve pairing statins with PCSK9 inhibitors or other agents like ezetimibe, mipomersen, lomitapide, and LDL apheresis [3].

4. Lipoprotein Apheresis

Lipoprotein apheresis is a nonsurgical therapy that filters the blood to remove excess LDL cholesterol. This treatment is often performed every 2-3 weeks for severe cases of FH [7].

5. Other Medications

Other medications, such as ezetimibe and mipomersen, may be prescribed in combination with statins or PCSK9 inhibitors to further lower LDL cholesterol levels.

It's essential to note that the choice of medication and treatment regimen depends on individual factors, including age, severity of FH, and presence of other health conditions. A healthcare provider will determine the most suitable treatment plan for each patient.

References: [1] Context 1 [2] Context 2 [3] Context 3 [7] Context 7

Familial hypercholesterolemia (FH) has several differential diagnoses, which are conditions that can present with similar symptoms and characteristics, making it challenging to diagnose FH accurately. Some of the key differential diagnoses for FH include:

• Dysbetahyperlipoproteinemia (type III hyperlipidemia): This is a rare genetic disorder characterized by elevated levels of triglycerides and cholesterol in the blood [2].
• Familial ligand defective apoB-100, familial defective apoB-100: These are genetic variants that affect the apolipoprotein B gene, leading to high levels of LDL cholesterol in the blood [2].
• Severe heterozygous FH: This is a form of FH where an individual inherits one mutated copy of the LDLR gene from one parent and has significantly elevated levels of LDL cholesterol [8].
• Sitosterolemia: This is a rare genetic disorder characterized by high levels of plant sterols in the blood, which can mimic the symptoms of FH [8].
• Lysosomal acid lipase deficiency: This is a genetic disorder that affects the breakdown of triglycerides and cholesterol in the body, leading to elevated levels of these lipids in the blood [8].

It's essential to note that differential diagnoses for FH are not exhaustive, and other conditions may also be considered based on individual patient characteristics.

References: [2] - Mar 13, 2024 [8] - Oct 8, 2024