1. Understanding Familial Hypercholesterolemia: Causes, Symptoms, & Treatment

Familial hypercholesterolemia (FH) is a genetic disorder. People with FH are born with high LDL cholesterol which is the "bad" cholesterol that can block your arteries. Everyone's cholesterol levels tend to rise with age. However, those with FH have LDL levels that start high and get higher over time. A healthy LDL level is less than 100 mg/dL (milligrams per deciliter), but people with familial hypercholesterolemia can have an LDL of 160 mg/dL to 400 mg/dL or higher.
 

2. Genetic Causes & Early Intervention in Familial Hypercholesterolemia

Familial hypercholesterolemia is commonly caused by a mutation in the gene for the LDL cholesterol receptor, which is involved in passing LDL from the blood into cells for use by, or removal from, the body. Mutations in other genes also can cause inherited high cholesterol. If you have FH, finding the disorder early and treating it can reduce your risk of heart disease by about 80%. If your child is diagnosed with FH, statin therapy in childhood may be required, often starting by age 8-10.
 

3. Genetic Factors Contributing to FH

FH will result from mutations in several genes, including:
1. LDL Receptor Genes
Most people with FH fault one of these genes. It means you don't have enough LDL receptors, so cholesterol builds up in the blood.
2. APOB Gene (Apolipoprotein B)
Only two or three out of every 100 people with FH are diagnosed with this gene. It means LDL cholesterol can't bind well to LDL receptors. LDL is taken out of the blood too slowly, and blood cholesterol stays high.
3. PCSK9 Gene
Only a few people have this type of FH. A fault with this gene means that LDL receptors are broken down in the liver, so they can't take cholesterol out of your blood.
 

4. Recognizing the Symptoms of Familial Hypercholesterolemia

Your doctor may be able to detect physical signs of FH during a clinical exam, although not everyone with FH has these signs. These physical signs of FH occur when extra cholesterol builds up in different parts of the body:
1. Bumps or lumps around your knees, knuckles, or elbows
2. Swollen or painful Achilles tendon
3. Yellowish areas around your eyes
4. A whitish-gray color in the shape of a half-moon on the outside of your cornea
 

5. Underlying Causes of Familial Hypercholesterolemia

Familial hypercholesterolemia is a disease you inherit or get from one or both of your parents. In people with this genetic issue, a specific protein (LDL receptor) that gets LDL out of your blood doesn't work well, or there isn't enough of it. The cholesterol buildup in your arteries is like what would happen if you didn't take your trash out of your house on a regular basis. It would just keep piling up until you couldn't find a path through it. When cholesterol fills your arteries, your blood can't get through.
 

6. Types of FH & Their Implications

There are two main types of FH:
1. Heterozygous FH (HeFH): It is the more common type and is inherited from one parent. In severe cases, LDL cholesterol levels can reach above 190 milligrams per deciliter (mg/dL) of blood. If left untreated, people with HeFH may develop heart disease as early as 30 years old.
2. Homozygous FH (HoFH): It's a rare form and is inherited from both parents. LDL cholesterol levels can reach above 400 mg/dL of blood. If not detected and treated early, people with HoFH may develop heart disease in the first 10 years of life, sometimes as early as 2 or 3 years old. Learn more about HoFH.
 

7. Diagnostic Tests for Familial Hypercholesterolemia

Healthcare providers generally use two diagnostic tests:
1. Your provider will want to do a lipid panel blood test to measure your cholesterol. Children with familial hypercholesterolemia can have LDL levels higher than 160 mg/dL. Adults can have LDL of 190 mg/dL or higher. In people with a severe form of homozygous familial hypercholesterolemia, LDL can be higher than 400 mg/dL. For all ages, a healthy LDL level is less than 100 mg/dL.
2. A DNA test can find problems with one of the three genes that can cause FH.
 

8. Management Strategies and Treatment Options

Effective management of FH involves:
1. Eating less saturated fat.
2. Not eating trans fats.
3. Eating less cholesterol.
4. Getting protein from vegetables, fish, lean poultry and low-fat dairy foods.
5. Eating more soluble fiber.
6. Eating lots of vegetables, nuts, legumes, fruit and whole grains.
7. Not eating egg yolks
 

9. Medications for Lowering Blood Cholesterol Levels

Other types of medicines can be used to lower blood cholesterol levels either instead of or as well as statins. These are:
1. Ezetimibe
2. PCSK9 inhibitors such as alirocumab and evolocumab
3. Bempedoic acid
4. Inclisiran