Familial Hypercholesterolemia (FH)
What is Familial Hypercholesterolemia (FH)?
Familial hypercholesterolemia is an inherited genetic condition that causes extremely high cholesterol levels from birth. People with FH have defects in the LDL receptor gene, which means their cells cannot properly remove LDL cholesterol from the bloodstream. This causes cholesterol to build up in the blood and deposit in arteries and tissues.
FH affects roughly 1 in 250 people worldwide, making it one of the most common genetic disorders. Most people have heterozygous FH, meaning they inherited one faulty gene copy from one parent. A smaller number have homozygous FH, inheriting faulty genes from both parents, which causes much more severe disease. Without treatment, people with FH face a significantly higher risk of early heart attacks and cardiovascular disease.
The condition is often silent in childhood and young adulthood. Many people discover they have FH only after a heart attack or during routine cholesterol screening. Early diagnosis and treatment can prevent most cardiovascular complications and help people with FH live normal, healthy lives.
Symptoms
- Very high LDL cholesterol levels, often above 190 mg/dL in adults
- Cholesterol deposits under the skin, called xanthomas, especially on knuckles, elbows, or knees
- Cholesterol deposits around the eyes, called xanthelasmas
- Cholesterol deposits in the cornea, creating a gray or white arc called corneal arcus
- Chest pain or angina due to early coronary artery disease
- Heart attack at a young age, sometimes before age 40 in men or 50 in women
- Family history of high cholesterol or early heart disease
Many people with FH have no symptoms at all, especially in childhood and early adulthood. The condition is often discovered only through blood testing or after a cardiac event. This is why family screening is so important when FH is diagnosed in one person.
Concerned about Familial Hypercholesterolemia (FH)? Check your levels.
Screen for 1,200+ health conditions
Causes and risk factors
FH is caused by mutations in genes that control how the body processes cholesterol. The most common mutations affect the LDL receptor gene, which normally helps remove LDL cholesterol from the blood. Other mutations can affect the Apolipoprotein B gene or the PCSK9 gene. These genetic defects are passed from parents to children in an autosomal dominant pattern, meaning just one faulty gene copy is enough to cause the condition.
Risk factors include having a parent or sibling with FH, a family history of early heart disease, or very high cholesterol levels that do not respond well to diet alone. Because FH is genetic, lifestyle factors like diet and exercise do not cause the condition, though they can affect how severe it becomes. Some ethnic groups, including French Canadians, Ashkenazi Jews, and certain populations in South Africa and the Netherlands, have higher rates of FH due to founder effects.
How it's diagnosed
FH is diagnosed through a combination of blood tests, physical examination, and family history. Doctors look for very high LDL cholesterol levels, typically above 190 mg/dL in adults or above 160 mg/dL in children. Apolipoprotein B testing helps confirm the diagnosis, as people with FH typically have Apo B levels above 130 mg/dL. Physical signs like xanthomas or corneal arcus also support the diagnosis.
Genetic testing can identify the specific mutation causing FH, which is useful for family screening. Rite Aid offers Apolipoprotein B testing as an add-on to help detect and monitor FH. Once diagnosed, family members should also be tested, as FH runs in families and early detection prevents complications. Testing is especially important for children in affected families, as treatment can begin early.
Treatment options
- Statin medications to lower LDL cholesterol, often at high doses
- Ezetimibe to reduce cholesterol absorption in the intestines
- PCSK9 inhibitors for patients who need additional cholesterol lowering
- Bile acid sequestrants to help remove cholesterol from the body
- Heart-healthy diet low in saturated fat and trans fat
- Regular physical activity, aiming for at least 150 minutes per week
- Avoiding smoking and limiting alcohol intake
- Regular monitoring of cholesterol levels and heart health
- For severe cases, LDL apheresis to physically remove cholesterol from the blood
Need testing for Familial Hypercholesterolemia (FH)? Add it to your panel.
- Simple blood draw at your nearest lab
- Results in days, not weeks
- Share results with your doctor
Frequently asked questions
Regular high cholesterol usually develops over time due to diet, lifestyle, and aging. FH is an inherited genetic condition present from birth that causes extremely high cholesterol regardless of lifestyle. People with FH typically have cholesterol levels much higher than those with common high cholesterol, often above 190 mg/dL even with healthy habits.
Yes, children can inherit FH from their parents and have high cholesterol from birth. Testing is recommended for children as young as 2 years old if a parent has FH. Early diagnosis allows for lifestyle changes and sometimes medication to prevent heart disease later in life. Children with FH may need treatment starting around age 8 to 10.
FH follows an autosomal dominant inheritance pattern. If one parent has FH, each child has a 50% chance of inheriting the condition. If both parents have FH, the risk is much higher and children may inherit a more severe form. Genetic counseling can help families understand their risk and plan for testing.
Xanthomas are yellowish cholesterol deposits that form under the skin, often on the knuckles, elbows, knees, or Achilles tendons. They occur because cholesterol levels are so high in FH that the excess begins depositing in tissues. Not everyone with FH develops xanthomas, but their presence is a strong indicator of the condition and suggests the need for more intensive treatment.
Apolipoprotein B is a protein found on LDL cholesterol particles. Each LDL particle has one Apo B molecule, so measuring Apo B gives an accurate count of harmful cholesterol particles. People with FH typically have Apo B levels above 130 mg/dL, which helps confirm the diagnosis and monitor treatment response.
Diet and exercise are important but rarely sufficient to treat FH alone. Because FH is caused by genetic defects in cholesterol processing, most people need medication to reach safe cholesterol levels. A heart-healthy diet and regular exercise do help lower cholesterol somewhat and reduce overall cardiovascular risk, so they remain essential parts of treatment alongside medication.
Treatment timing depends on cholesterol levels and other risk factors. Many children with FH start statin therapy between ages 8 and 10. Adults diagnosed with FH should begin treatment immediately to prevent heart disease. The earlier treatment starts, the better the long-term outcomes, as it prevents years of cholesterol damage to arteries.
With early diagnosis and proper treatment, people with FH can have normal life expectancies. Untreated FH significantly shortens lifespan due to early heart attacks and cardiovascular disease. Men with untreated FH often have heart attacks before age 50, and women before age 60. Statin therapy and lifestyle changes reduce this risk dramatically when started early.
Yes, all first-degree relatives should be tested when someone is diagnosed with FH. This includes parents, siblings, and children. Cascade screening helps identify other family members with the condition so they can start treatment early. About half of first-degree relatives will also have FH if you do, making family screening one of the most important steps after diagnosis.
Homozygous FH occurs when someone inherits faulty genes from both parents, making it much more severe than typical FH. It affects about 1 in 300,000 people and causes cholesterol levels above 500 mg/dL. People with homozygous FH may have heart attacks in childhood or teenage years and need intensive treatment, including medications, LDL apheresis, or even liver transplant in severe cases.