Familial Hypercholesterolemia – Symptoms and Causes
Overview
Familial hypercholesterolemia is a genetic condition that disrupts normal cholesterol processing in the body. People with this condition face higher risks of heart disease and may experience heart attacks at younger ages than the general population.
The condition is present at birth, though symptoms might not become noticeable until adulthood. This hereditary disorder passes through families via genetic changes.
In rare cases, individuals inherit the condition from both parents, resulting in a more severe form that typically shows symptoms during childhood. Without proper treatment, this severe variant often leads to death before age 20.
Signs and Symptoms
Skin Changes
Familial hypercholesterolemia (FH) often causes visible skin signs. Many people develop yellowish patches called xanthomas. These fatty deposits can appear around the eyes, elbows, or on the tendons.
Some patients get yellowish bumps on their eyelids, known as xanthelasma. These skin changes happen when extra cholesterol builds up in the body. They might show up in childhood for people with more severe forms of FH.
Tendon Abnormalities
Tendon xanthomas are a key sign of this condition. These are hard, painless lumps that form on tendons, especially those in the:
- Back of the heel (Achilles tendon)
- Hands
- Knees
- Elbows
These lumps develop when cholesterol collects in the tendons. Doctors often check for these lumps during physical exams. The presence of tendon xanthomas strongly suggests FH, particularly when paired with high cholesterol levels.
Eye-Related Findings
Eye changes can occur in people with familial hypercholesterolemia. A corneal arcus (a white, gray, or blue ring around the cornea) may develop. In younger patients, this ring is an important warning sign of FH.
Eye doctors might notice it during routine exams. Some patients also develop xanthelasma on their eyelids, which appear as flat, yellowish growths. These don’t usually affect vision but serve as visible markers of high cholesterol levels.
Causes
Familial hypercholesterolemia (FH) is mainly caused by gene mutations that affect how the body processes cholesterol. These genetic defects lead to abnormally high levels of LDL (low-density lipoprotein) cholesterol in the blood from birth.
The most common cause of FH is mutations in the LDLR gene, which provides instructions for making the LDL receptor protein. This receptor helps remove LDL cholesterol from the bloodstream. When the receptor doesn’t work properly, LDL builds up in the blood.
Other genetic mutations that can cause FH include:
- APOB Gene: Creates apolipoprotein B-100, which helps LDL receptors bind with LDL cholesterol.
- PCSK9 Gene: Makes a protein that breaks down LDL receptors.
- LDLRAP1 Gene: Helps LDL receptors work properly.
FH follows different inheritance patterns:
| Type | Inheritance Pattern | Risk |
|---|---|---|
| Heterozygous FH | Inherited from one parent | 1 in 250 people |
| Homozygous FH | Inherited from both parents | Much rarer (about 1 in 300,000) |
People with heterozygous FH have LDL cholesterol levels twice the normal amount, while those with homozygous FH may have levels four times higher than normal.
Unlike typical high cholesterol that develops later in life due to lifestyle factors, FH is present from birth and causes high cholesterol even in people who eat healthy diets and exercise regularly.
Risk Factors
Familial hypercholesterolemia (FH) occurs due to specific genetic factors that increase a person’s chance of developing this condition. The main risk factor is having a family history of FH, as the condition passes from parents to children.
If one parent has FH, each child has a 50% chance of inheriting the condition.
Certain ethnic groups show higher rates of FH. People with French Canadian, Lebanese, Finnish, and Ashkenazi Jewish ancestry face greater risks due to what scientists call the “founder effect,” where specific gene mutations become common in isolated populations.
Untreated FH significantly increases the risk of early heart disease. Men with FH may develop heart problems by their 40s or 50s, while women typically develop them about 10 years later.
People with the more severe homozygous FH (inheriting mutations from both parents) may develop heart disease in childhood.
Complications
Familial hypercholesterolemia (FH) can lead to several serious health problems if left untreated. The most concerning complication is early heart disease.
Atherosclerosis occurs when cholesterol builds up in artery walls, forming plaques that narrow blood vessels. This process happens faster in people with FH. The reduced blood flow can affect many parts of the body, including the heart, brain, and limbs.
Heart-related complications include:
- Heart attacks (sometimes before age 40 in men and 50 in women)
- Chest pain (angina)
- Coronary artery disease
- Heart valve problems
Stroke risk increases significantly in people with untreated FH. This happens when a clot blocks blood flow to part of the brain or when a blood vessel in the brain bursts.
People with FH may develop visible signs of cholesterol deposits. These include yellowish patches called xanthomas around the eyes, tendons, knees, elbows, and sometimes hands. Cholesterol can also create a white arc near the colored part of the eye.
Peripheral artery disease may develop as arteries in the legs become narrowed or blocked. This causes pain when walking and can lead to poor circulation in the limbs.
