Published: 18 Jun 2025

ICD9: 272.0      ICD10: E78.0      ICD11: 5C80.0

Familial Hypercholesterolemia (FH) is a genetic disorder that causes high levels of low-density lipoprotein (LDL) cholesterol, often referred to as "bad" cholesterol, in the blood.
This high cholesterol level starts from birth and can lead to early and aggressive buildup of plaque in the arteries (atherosclerosis), significantly increasing the risk of heart disease, heart attacks, and strokes at a much younger age than the general population.

Here's a breakdown of key aspects of FH:

What it is:

Genetic Disorder: FH is primarily caused by a mutation in one of several genes that control how the body handles cholesterol. These genes usually code for proteins involved in LDL receptor function or LDL metabolism.
High LDL Cholesterol: The primary characteristic of FH is consistently elevated LDL cholesterol levels. These levels are often significantly higher than normal, even with a healthy diet and lifestyle.
Early Heart Disease Risk: Due to the high LDL cholesterol, people with FH have a much higher risk of developing heart disease at a younger age, often in their 30s, 40s, or 50s, even without other risk factors like smoking or high blood pressure.

Causes:

Gene Mutations: The most common gene mutations involved in FH affect:
*LDLR* (Low-Density Lipoprotein Receptor): This gene provides instructions for making the LDL receptor, which helps remove LDL cholesterol from the blood. Mutations here often result in the receptor not working properly, leading to high LDL levels.
*APOB* (Apolipoprotein B): This gene provides instructions for making apolipoprotein B, a protein that binds to LDL cholesterol. Mutations can prevent LDL from binding to the LDL receptor efficiently.
*PCSK9* (Proprotein Convertase Subtilisin/Kexin Type 9): This gene makes a protein that degrades LDL receptors. Mutations that increase PCSK9 activity lead to fewer LDL receptors and higher LDL levels.
*LDLRAP1*: This gene provides instructions for making a protein that helps LDL receptors function properly.

Types:

Heterozygous FH: This is the more common form, where a person inherits one copy of the mutated gene from one parent and one normal copy from the other parent. People with heterozygous FH typically have LDL cholesterol levels that are about twice as high as normal.
Homozygous FH: This is a much rarer and more severe form, where a person inherits two copies of the mutated gene (one from each parent). People with homozygous FH have extremely high LDL cholesterol levels and often develop severe heart disease in childhood or adolescence.

Symptoms:

Often Asymptomatic: Many people with FH have no noticeable symptoms until they develop heart disease. This is why early screening and diagnosis are crucial.
Possible Physical Signs (less common):
Xanthomas: Cholesterol deposits under the skin, often around the tendons (especially on the Achilles tendon, elbows, and knuckles).
Xanthelasma: Yellowish cholesterol deposits around the eyelids.
Corneal Arcus: A whitish-gray ring around the cornea of the eye.

Diagnosis:

Lipid Panel (Blood Test): Measures LDL cholesterol, HDL cholesterol, triglycerides, and total cholesterol. Consistently high LDL levels are a primary indicator.
Family History: A strong family history of high cholesterol and early heart disease is a significant clue.
Genetic Testing: Can confirm the diagnosis by identifying the specific gene mutation responsible for FH. Genetic testing is often recommended when clinical findings suggest FH but are not definitive, or when cascade screening of family members is desired. It can also help determine the severity of the condition.
Dutch Lipid Clinic Network Criteria: A scoring system that combines LDL cholesterol levels, family history, and physical findings to assess the likelihood of FH.

Treatment:

Lifestyle Modifications:
Healthy Diet: Low in saturated and trans fats, cholesterol, and processed foods. Focus on fruits, vegetables, whole grains, and lean protein.
Regular Exercise: Helps improve cholesterol levels and overall cardiovascular health.
Weight Management: Maintaining a healthy weight can also improve cholesterol levels.
Smoking Cessation: Smoking significantly increases the risk of heart disease.
Medications:
Statins: The most common medication used to lower LDL cholesterol. They work by blocking an enzyme in the liver that produces cholesterol.
Ezetimibe: Reduces the absorption of cholesterol from the small intestine.
PCSK9 Inhibitors: Newer injectable medications that significantly lower LDL cholesterol by blocking the PCSK9 protein (which breaks down LDL receptors).
Bempedoic acid: Another newer medication that inhibits cholesterol synthesis and can be used in combination with statins.
Lipid Apheresis: A procedure similar to dialysis that removes LDL cholesterol from the blood. This is typically reserved for people with homozygous FH or those who do not respond well to other treatments.

Importance of Early Diagnosis and Treatment:

Early diagnosis and treatment of FH are crucial to preventing or delaying the onset of heart disease. With proper management, people with FH can live long and healthy lives.

Screening:

Universal Screening: Some organizations recommend universal cholesterol screening in children and adolescents.
Targeted Screening (Cascade Screening): Screening family members of individuals diagnosed with FH is highly recommended. This "cascade screening" is a cost-effective way to identify other affected individuals who may be unaware of their condition.

In summary, Familial Hypercholesterolemia is a serious genetic disorder that causes high cholesterol and significantly increases the risk of early heart disease. Early diagnosis and aggressive treatment are essential for managing the condition and preventing cardiovascular complications. If you have a family history of high cholesterol or early heart disease, talk to your doctor about getting screened for FH.