Cause, Signs, and Treatment of Familial Hypercholesterolemia

the Family Heart Foundation is the only organization exclusively dedicated to raising awareness of familial hypercholesterolemia, or FH, in the United States. FH is a genetic disorder that goes largely undiagnosed and untreated. While 1 in every 300-500 people worldwide is thought to have the genetic abnormality, in the United States only 10% of those cases have been diagnosed . Effective treatments are available for FH.  Because FH leads to aggressive and premature cardiovascular disease, this lack of accurate diagnoses and treatment poses a severe health risk to the millions of undiagnosed people in the world.

Cause of Familial Hypercholesterolemia

FH is caused by a genetic mutation in the liver’s receptors for low density lipoproteins (LDL), commonly known as bad cholesterol.  People with FH do not have the ability to clear LDL Cholesterol from their bodies like other people do, so it builds up in their blood.  People with FH are born with elevated LDL levels and are exposed over a lifetime to persistently high levels, resulting in a 20-fold greater risk of early coronary artery disease than the general population.

Though some genetic abnormalities develop over time due to external factors, the genetic mutation causing FH is only inherited. It is an autosomal dominant trait, which means that if a child inherits the abnormal gene from one parent, the child will have heterozygous FH.  Each child of a person with FH has a 50% chance of inheriting FH.  If a child receives the mutation from both parents, however, the child will have a more severe form of the disease called homozygous FH.

Signs of Familial Hypercholesterolemia

Too often, the first sign that a person has FH is a cardiac event.  Until then, FH is often asymptomatic and undiagnosed.  The most important sign of FH is abnormally high LDL (above 190 mg/dL in adults and above 160 mg/dL in children).  Some FH patients do exhibit outwards symptoms, including xanthomas and xanthelasmas (yellowish bumps on the skin which are deposits of excess cholesterol) or corneal arcus (a greyish arc around the cornea of the eye).  But many people with FH do not exhibit these symptoms.

FH can be diagnosed by a doctor based on elevated LDL Cholesterol and family history.  If LDL is above 190 for adults, or above 160 for children, and there is a family history of heart disease and elevated cholesterol, a patient should be evaluated for familial hypercholesterolemia.  Genetic testing is not necessary for the diagnosis of FH.  While it is possible to test for some of the genetic mutations that cause FH, other genetic mutations have not yet been identified so genetic tests will result in many false negatives.  A clinical diagnosis based on LDL and family history is sufficient.

Treatment of Familial Hypercholesterolemia

For people with heterozygous familial hypercholesterolemia, lifestyle changes are an important first step.  Like everyone else, FH patients should follow a healthy diet, exercise regularly, and manage their weight. But a key characteristic of FH is that lifestyle changes will not be sufficient to lower your cholesterol. Your doctor will prescribe medication such as a statin to help lower your cholesterol.  In many cases, more than one medication may be necessary to achieve optimal LDL levels.  In very difficult cases, your doctor may also want you to try apheresis, a treatment where blood is removed from your body, LDL is filtered out, and then the blood is returned to your system.  It is important to work with your healthcare provider to find the treatment that works best for you.

Homozygous FH requires more extensive treatment. If you are diagnosed with homozygous FH, apheresis is likely to be part of your treatment from the start.  There are several promising treatments coming on the market to treat homozygous FH patients as well as heterozygous FH patients for whom statins are not sufficient.  In rare cases, homozygous FH patients may receive liver transplants.

Cascade Screening for Familial Hypercholesterolemia

FH is an inherited disorder – it runs in families. If you are diagnosed with FH, there is a 100% chance that at least one of your parents has the disorder too, and that means that other members of your immediate and extended family may have the genetic mutation as well. Once someone is diagnosed with FH, screening family members, know as cascade screening, can be used to identify relatives who have it too.  Early diagnosis and treatment can dramatically lower the risk of early heart disease in people with FH.  If you have been diagnosed with FH, you can help your family members by encouraging them to be evaluated based on their LDL levels and family history.

Because we are still learning about the prevalence of FH and looking for ways to improve diagnosis and treatment, the Family Heart Foundation has created a registry to help patients stay informed and help doctors and researchers track the disease and learn from patients like you.

To learn more about FH, contact the Family Heart Foundation today.

One Response to “Cause, Signs, and Treatment of Familial Hypercholesterolemia”

  1. Judy Lewis

    I have been on medication for more than 10 years and with changing my diet, only one year was I able to lower my levels to 194, they seem to stay at 220-234 I have been on lipator. Any suggestions. The statin cause painful leg cramps too.


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