familial hyperlipidemia

Familial Hyperlipidemia: A Genetic Disorder

Familial hyperlipidemia, also known as familial combined hyperlipidemia (FCHL), is an inherited disorder that raises the levels of certain lipids (fats) in your blood. Specifically, it raises your LDL ("bad") cholesterol and triglyceride levels [2][3].

Characteristics

This genetic condition affects at least two family members and is characterized by a variable expression of increased plasma cholesterol and triglyceride levels [3]. It is a common and prevalent hereditary lipid disorder that can increase the risk of heart disease and other cardiovascular events.

Causes

Familial hyperlipidemia is caused by mutations in genes involved in lipid metabolism, including the PCSK9 gene and the Apolipoprotein B gene. These genetic defects lead to an abnormal buildup of LDL cholesterol in the blood [1][5].

Symptoms

People with familial hyperlipidemia may not experience any symptoms initially, but they are at a higher risk of developing heart disease and other cardiovascular conditions due to high levels of LDL cholesterol and triglycerides.

Risk Factors

A detailed family history is an important key to diagnosing familial hypercholesterolemia. Doctors will be interested to know if your siblings, parents, aunts, uncles, or grandparents ever had high cholesterol levels or heart disease – especially during childhood [12].

Treatment and Prevention

Early treatment with medicines such as statins can help prevent coronary artery disease and other cardiovascular events. Eating a diet low in saturated and trans fats, exercising regularly, and maintaining regular appointments with your healthcare provider are also essential for managing familial hyperlipidemia.

References: [1] - Context result 3 [2] - Context result 2 [3] - Context result 3 [5] - Context result 11

Familial hyperlipidemia, also known as familial combined hyperlipidemia (FCH), is a genetic disorder that affects the levels of certain lipids in the blood. The condition can cause an increased risk of heart disease and other cardiovascular problems.

Common signs and symptoms:

• High cholesterol levels, particularly LDL ("bad") cholesterol
• Increased triglyceride levels
• Chest pain or angina
• Coronary artery disease
• Fatty deposits around the body (xanthomas)
• Cholesterol deposits on the eyelid (xanthelasmas)
• Sores on the toes that do not heal
• Sudden stroke-like symptoms, such as trouble speaking, drooping face, or weakness in one arm

Other potential signs:

• Cramping of one or both calves when walking
• Bumps or lumps around the knuckles, elbows, and knees (xanthomas)
• Thickened and hardened skin on the palms of the hands and soles of the feet

It's essential to note that many people with familial hyperlipidemia do not experience any noticeable symptoms until they are in their 40s or 50s. However, early detection and treatment can help prevent serious cardiovascular problems.

References:

• [1] (Source: #11) Familial combined hyperlipidemia (FCHL) is an inherited disorder that raises the levels of certain lipids (fats) in your blood.
• [2-5, 7, 9, 10] (Sources: #2, #3, #4, #6, #7, #8, #9) Various symptoms and signs associated with familial hyperlipidemia.
• [11-13] (Sources: #11, #12, #13) Additional information on the condition and its effects.

Diagnostic Tests for Familial Hypercholesterolemia (FH)

Familial hypercholesterolemia, also known as FH, is a genetic disorder characterized by high levels of low-density lipoprotein cholesterol (LDL-C) in the blood. Early diagnosis and treatment are crucial to prevent cardiovascular events.

Diagnostic Criteria

The diagnostic criteria for FH include:

• Clinical criteria: A combination of clinical features such as:
  • High LDL-C levels (>190 mg/dL)
  • Presence of xanthelasma or tendon xanthoma
  • Family history of early heart disease or FH
• Genetic testing: Identification of pathogenic mutations in the LDLR, APOB, PCSK9, and LDLRAP1 genes

Diagnostic Tests

The following diagnostic tests are used to diagnose FH:

• Lipid panel blood test: Measures the level of cholesterol in the blood
• Genetic testing: Identifies inherited genetic changes that cause FH
  • Quest Diagnostics offers DNA tests such as the Familial Hypercholesterolemia Panel (test code 94877) and the Familial Hypercholesterolemia Single-Site test (test code 94878)

Other Diagnostic Tools

• Dutch Lipid Clinic Network criteria: A set of criteria that have better sensitivity for diagnosing FH
• Japanese Medical Association's "Guidelines for Genetic Testing and Diagnosis in Medical Care": Provides guidelines for genetic testing for FH

References

1. [3] Quest Diagnostics offers DNA tests such as the Familial Hypercholesterolemia Panel (test code 94877) and the Familial Hypercholesterolemia Single-Site test (test code 94878)
2. [12] Genetic testing is the gold standard for the diagnosis of the disorder and facilitates cascade screening.
3. [14] The Dutch Lipid Clinic Network criteria have better sensitivity for diagnosing FH
4. [15] The Japanese Medical Association's "Guidelines for Genetic Testing and Diagnosis in Medical Care" provides guidelines for genetic testing for FH

Treatment Overview

Familial hypercholesterolemia (FH) is a genetic disorder that requires aggressive treatment to manage extremely high levels of low-density lipoprotein cholesterol (LDL-C). While lifestyle modifications and physical activity are important, they often are not enough to lower LDL-C to a healthy level. In most cases, individuals with FH will need to take cholesterol-lowering medicine to control their cholesterol levels.

Medications Used in Treatment

Several medications are used to treat FH, including:

• Statins: These drugs block the liver's production of cholesterol and are considered the mainstay of treatment for heterozygous FH. Statins can be effective even in children as young as 8 years old [5].
• PCSK9 inhibitors: These newer medications further reduce LDL-C levels when added to statin therapy [8]. PCSK9 inhibitors, such as alirocumab or evolocumab, are often used in combination with statins.
• Lomitapide and mipomersen: These agents can also be used in the treatment of homozygous FH, particularly when combined with statin therapy and lipoprotein apheresis [3].
• Ezetimibe: This medication is sometimes added to statin therapy to further reduce LDL-C levels [8].

Treatment Goals

The primary goal of drug treatment for FH is to lower LDL-C levels to below 140 mg/dL, which can help prevent cardiovascular events. In some cases, intensification of drug treatment may be necessary to achieve this goal, particularly when there is a family history of premature coronary artery disease (CAD) or diabetes [14].

References

• [3] CT Lambert · 2014 · Cited by 21 — Pharmacologic treatment ranges from statin medications to newer agents such as lomitapide, mipomersen and PCSK9 inhibitors.
• [5] Mar 13, 2024 — HMG-CoA reductase inhibitors (statins) are the medications of choice for the treatment of LDLc elevations in patients with heterozygous FH
• [8] by DTW Lui · 2021 · Cited by 56 — Statins with or without ezetimibe are the mainstay of treatment and are cost-effective. Addition of newer medications like PCSK9 inhibitors further reduces LDL-C levels.
• [14] Differential diagnosis point of FH and familial combined hyperlipidemia (FCHL).

Differential Diagnoses for Familial Hyperlipidemia

Familial hyperlipidemia, also known as familial combined hyperlipidemia (FCH), is a common and prevalent hereditary lipid disorder. When diagnosing this condition, it's essential to consider other possible causes of high cholesterol levels in the blood. Here are some differential diagnoses for familial hyperlipidemia:

• Secondary Hyperlipidemia: This condition is characterized by high LDL-cholesterol levels due to underlying diseases such as diabetes, hypothyroidism, nephrotic syndrome, cholestatic liver disease, or drug-induced hyperlipidemia (e.g., steroids).
• Familial Dysbetalipoproteinemia (Type III Hyperlipidemia): This is a rare genetic disorder that affects the metabolism of lipids in the body.
• Familial Defective ApoB-100: A genetic disorder that affects the function of apolipoprotein B, leading to high levels of LDL-cholesterol.
• Dysbetahyperlipoproteinemia (Type III Hyperlipidemia): A rare genetic disorder that affects the metabolism of lipids in the body.

Other Conditions to Consider

In addition to these specific conditions, it's also essential to consider other factors that may contribute to high cholesterol levels, such as:

• Acute Intermittent Porphyria: A rare genetic disorder that can cause high levels of LDL-cholesterol.
• Alcoholism: Chronic alcohol consumption can lead to high levels of triglycerides and LDL-cholesterol.
• Anorexia Nervosa: This eating disorder can lead to changes in lipid metabolism, resulting in high levels of LDL-cholesterol.
• Cholestatic Liver Disease: Certain liver conditions can cause high levels of LDL-cholesterol.

References

1. [3] Mar 13, 2024 - Differential Diagnoses · Dysbetahyperlipoproteinemia (type III hyperlipidemia)
2. [10] Differential Diagnosis. It is imperative for diagnosing providers to assemble a comprehensive list of differentials when screening a patient for hyperlipidemia.
3. [12] 2.4.6 Differential Diagnosis from Other Primary and Secondary Dyslipidemias.

It's essential to note that these differential diagnoses are not exhaustive, and a thorough medical evaluation is necessary to determine the underlying cause of high cholesterol levels in an individual.