Diabetes and Lipid Clinic of Alaska



Familial Hypercholesterolemia

People who have very high LDL (usually over 190mg/dL), are much more likely to have an inherited form of high cholesterol called "familial hypercholesterolemia" (FH).
In the United States, about 1 in 500 people have FH. People with FH are unable to control their cholesterol levels with diet alone. They usually need relatively high doses of cholesterol-lowering drugs combined with other therapies, such as LDL apheresis.

FH and Heart Disease

Anyone with high LDL has a higher-than-average chance that cholesterol is sticking to the inside of his or her arteries. This is called "plaque". Plaque buildup can block blood flow to the heart or other parts of the body.  When the blockage gets serious enough, it can cause a heart attack.

When FH isn't diagnosed and treated early, there is a much higher risk of heart disease — especially at an unusually young age. On average, men with FH have a 50 times higher risk of having a heart attack before they are 40 than a man without FH. A woman with FH has a 125 times higher risk. Even children with FH may have plaque buildup in their arteries.

Is Familial Hypercholesterolemia Inherited?

Familial hypercholesterolemia (FH) is hereditary, meaning it is usually passed from generation to generation. Hereditary diseases are caused by changes (called mutations) in our genes that cause them not to work normally. Our genes act as an instruction manual telling our bodies how to develop and function.

Genes come in pairs — we get one copy from our mother and one copy from our father. Only one gene in the pair needs to have a mutation in order for a person to have FH. This kind of inheritance is called "autosomal dominant".

When we have children, we pass one gene from each of our gene pairs on to our children. Our partner passes on the other set of genes. Because people with FH have one working gene and one non-working gene, each of their children have a 50% (half) chance that they will inherit the normal, working gene and won't have FH. But, each child also has a 50% (half) chance that they will inherit the non-working gene and will have FH.

How Do You Know If You Have Familial Hypercholesterolemia?

You may have FH if you have some combination of the following:

  • You have unusually high LDL cholesterol (often 190mg/dL or more). You may also have an unusually high level of total cholesterol (often over 290mg/dL)
  • You or a family member has had heart or blood vessel disease at an unusually young age (usually under 55 years old for men or 65 years old for women).
  • You or a family member have had fatty deposits in the skin, sometimes over the tendons (called "xanthomas")
  • You or a family member have had a collection of fat in the cornea of the eye (called "corneal arcus")

No Family History?

It is possible that you or another family member were the first to be diagnosed with FH. FH can happen for the first time in a family when a new gene mutation is formed in one person before they are born. When a new mutation happens, neither parent has an FH mutation, but that person's children still have a 50% chance for inheriting FH. The vast majority of people with FH inherited it from their parents. When there is no known family history, the most common reason is that other family members actually have FH and they just don't know about it yet.

Finding Familial Hypercholesterolemia with Cholesterol Testing

It can be difficult to diagnose FH with cholesterol testing alone. LDL levels alone aren't very specific for FH. For instance:

  • Some people, who don't have FH, do have very high levels of LDL cholesterol for other reasons.
  • Some people, who do have FH, don't have high enough levels of LDL cholesterol to raise the concern for FH.

LDL levels continue to climb as people with FH get older. Although young people with FH usually have higher than average LDL levels, they may not be high enough to consider FH. So, most people with FH unfortunately aren't diagnosed until they are middle-age, when damage from the high LDL cholesterol levels has already been done.

Benefits of Genetic Testing

Finding the actual gene mutation that causes FH can help both the person being tested and the extended family.
Benefits of finding an FH mutation with genetic testing:

  • Confirms the diagnosis of FH in a person with any other FH risk factor.

Most doctors agree that an FH mutation combined with any other risk factor is enough to make the diagnosis of FH. This is true even if the person with the FH mutation doesn't already have very high LDL levels. A risk factor might be a higher-than-usual LDL for the age, a family history of very high cholesterol or early heart disease, or xanthomas (fatty lumps in the skin).

  • May let the person with FH get earlier and better treatment.

The typical guidelines that doctors use to decide who has high cholesterol and how they should be treated don't work for people with FH. Lifestyle changes are rarely enough to control cholesterol levels. Certain drugs have been shown to lower cholesterol and prevent or shrink plaque buildup in people with FH. People with FH often need higher doses than usual of these drugs or combinations of drugs to get the LDL under control. The earlier treatment begins, the less damage is done and the lower the risk is for heart disease. In some cases, even children as young as 10 years old might be considered for treatment.

  • Alerts family members that they are at-risk at lets them get tested and treated early.

Studies have shown that for every person diagnosed with FH through genetic testing, 2 to 3 other relatives are also then found to have FH. These same studies also showed that only 40% to 50% of these relatives with FH were being treated for high cholesterol before genetic testing, but this increased to about 90% after testing.
A person who is tested and doesn't have the mutation that runs in the family has no higher chance of having FH than anyone else in the general population. These family members can avoid the frequent cholesterol testing that is needed when the diagnosis is unknown. Please see the information in this section for genetic testing.
For additional information, please contact the staff at the Diabetes and Lipid Clinic of Alaska.

Pros & Cons: Familial Hypercholesterolemia Testing

Everyone who is deciding whether to get genetic testing should first ask:

  • "Why am I getting tested?"
  • "What will this test mean for me?"
  • "What are the benefits of testing?"
  • "Are there any implications I should consider?"

These are very personal decisions. Before testing for familial hypercholesterolemia, we recommend you consider the medical and personal issues involved in testing.  Below are some of the things you should consider.


  • Testing by DNA sequencing will find the majority of gene mutations that can cause familial hypercholesterolemia (FH).
  • If you have signs of FH, finding a mutation confirms the diagnosis.
  • Finding a mutation makes genetic testing less expensive and much more accurate for other family members. Once a mutation is found, genetic testing can be used to make a diagnosis or rule-out the condition before symptoms even appear. Family members with a mutation can get the best screening and treatment possible and those without the mutation can avoid unnecessary screening.
  • Some people find genetic testing information useful when making personal decisions about such issues as insurance, employment, and family planning.


  • Genetic testing will not find all mutations that can cause FH.
  • If you are the first person in the family to be tested, a normal test result doesn’t rule out FH. If you are diagnosed based on your symptoms, a normal result doesn’t change your diagnosis. If you have no symptoms yet, you could still have FH even with a normal test result. You should still be screened and treated as anyone at-risk for the condition.
  • Insurance doesn’t always cover genetic testing and testing can be expensive.
  • You may have concerns about discrimination based on your results. There are laws that help protect most people from health insurance and employment discrimination. Genetic discrimination may also be a concern in getting life, disability, and long-term care insurance.
  • Genetic tests have the potential to reveal information about biological and non-biological relationships – especially when multiple family members are being tested.
  • Genetic test results can cause significant, and sometimes unexpected, emotional reactions. You could feel guilty or angry about having a genetic risk. Some people feel guilty about not having a genetic risk when other family members do. An abnormal test result could change your self-image or cause your loved ones to treat you differently. Consider trying to anticipate how a positive or negative result may make you, and those around you, feel.

National Library of Medicine and the National Institutes of Health. Medline Plus Review:
Familial Hypercholesterolemia. A brief and well-organized review of familial hypercholesterolemia — with pictures.
Link: http://www.nlm.nih.gov/MEDLINEPLUS/ency/article/000392.htm

National Human Genome Research Institute.

Learning About Familial Hypercholesterolemia. This site has a more complete discussion of familial hypercholesterolemia and provides many links to other high quality information sites.
Link: http://www.genome.gov/25520184

American Heart Association.
The American Heart Association has a wealth of information for both patients and professionals about a broad variety of heart disease topics. Start with the cholesterol overview page and explore from there.
Link: http://www.americanheart.org/

Make Early Diagnosis to Prevent Early Death:
For People With Inherited High Cholesterol. This non-profit organization was created to form a patient registry and identify people who are either undiagnosed or untreated for inherited cholesterol disorders, like familial hypercholesterolemia.
Link: http://www.medped.org/index.html

The information on this Web page is provided for educational purposes. You understand and agree that this information is not intended to be, and should not be used as, a substitute for medical treatment by a health care professional. You agree that Diabetes and Lipid Clinic of Alaska is not making a diagnosis of your condition or a recommendation about the course of treatment for your particular circumstances through the use of this Web page. You agree to be solely responsible for your use of information contained on this Web page

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