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Genetic and Rare Diseases Information Center (GARD)

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Familial hypercholesterolemia

*

* Not a rare disease

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Overview

What is familial hypercholesterolemia?

What are the signs and symptoms of familial hypercholesterolemia? 

How is familial hypercholesterolemia inherited?

How might familial hypercholesterolemia be treated?

What is familial hypercholesterolemia?

Familial hypercholesterolemia (FH) is an inherited condition that causes abnormally high levels of LDL (low density lipoprotein) cholesterol beginning at birth. When too much LDL cholesterol is present in the blood stream, it builds up in the walls of the arteries and increases the risk of heart attacks and heart disease. Men with FH may have heart attacks in their 40s to 50s, and women with FH may have them in their 50s to 60s.[1] FH is most commonly caused by mutations in the LDLR gene and is usually inherited in an autosomal dominant manner. More rarely, it may be caused by mutations in other genes and can be inherited in an autosomal recessive manner.[2] Treatment focuses on lowering LDL cholesterol levels in the blood and may include dietary modification and medication.[1]
Last updated: 10/22/2013

What are the signs and symptoms of familial hypercholesterolemia? 

Signs and symptoms in individuals with the autosomal dominant form of familial hypercholesterolemia (FH), also called the heterozygous form, may include:[3]

Men who have FH may have heart attacks in their 40s to 50s, and 85% of men with the disorder have a heart attack by age 60. Affected women may have heart attacks in their 50s and 60s.[1]

Individuals with the rare, autosomal recessive form of FH (also called homozygous FH) develop xanthomas beneath the skin over their elbows, knees and buttocks as well as in the tendons at a very early age, sometime in infancy.[1] In individuals with this form of FH, heart attacks and/or death may occur before age 30, sometimes in young children if they are not aggressively treated.[1][3]

Last updated: 10/22/2013

How is familial hypercholesterolemia inherited?

Familial hypercholesterolemia (FH) is usually inherited in an autosomal dominant manner (in which case it is referred to as heterozygous FH).[1] Individuals inherit two copies of each gene (one from each parent). In an autosomal dominant condition, having only one abnormal (mutated) copy of the gene is sufficient to cause the condition. In most cases the mutated gene is inherited from an affected parent, but it is possible for the mutation to occur for the first time in the affected individual. An individual with an autosomal dominant condition has a 50% (1 in 2) chance to pass the mutation on to each of his/her children and a 50% chance to not pass on the mutation.

More rarely, familial FH may be inherited in an autosomal recessive manner. This occurs when an individual inherits a mutated copy of the gene from both parents (this is also called homozygous FH). This is a much more severe form of FH. An individual with this form of FH will always pass on a mutated copy of the gene, and therefore each of his/her children will have heterozygous FH.[1]
Last updated: 10/22/2013

How might familial hypercholesterolemia be treated?

The overall goal of treatment for familial hypercholesterolemia (FH) is to lower the risk for atherosclerosis (build-up of plaque in the arteries) by lowering the LDL cholesterol levels in the blood stream. The first step in treatment for individuals with the heterozygous form (also called the autosomal dominant form) is changing the diet to reduce the total amount of fat eaten. This may be accomplished by limiting the amount of beef, pork, and lamb in the diet; cutting out butter, whole milk, fatty cheeses and oils; and eliminating egg yolks, organ meats and other sources of saturated fat from animals. Dietary counseling is often recommended to help individuals change their eating habits. Exercise and weight loss may also help in lowering cholesterol levels.

Drug therapy is also often necessary lifestyle changes may not be enough to lower cholesterol levels. Several different cholesterol-lowering medications may be used alone or in combination; they may include statinsbile acid sequestrants, ezetemibe, niacin, gemfibrozil, and fenofibrate.

Individuals with the more severe, homozygous form of FH (also called the autosomal recessive form) need more aggressive therapies to treat their significantly elevated levels of cholesterol. Drug therapy is often not effective enough at lowering LDL cholesterol levels. Therefore, individuals with this form may need periodical LDL apheresis, a procedure that removes LDL from the blood. In some cases, major surgery such as a liver transplant is necessary.[4]
Last updated: 10/22/2013

References
  1. Learning About Familial Hypercholesterolemia. NHGRI. March 23, 2011; http://www.genome.gov/25520184. Accessed 10/22/2013.
  2. Pascale Benlian. Familial hypercholesterolemia. Orphanet. July 2008; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=406. Accessed 10/22/2013.
  3. Familial Hypercholesterolemia. NORD. July 25, 2011; http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/811/viewAbstract. Accessed 10/22/2013.
  4. Learning About Familial Hypercholesterolemia. NHGRI. March 23, 2011; http://www.genome.gov/25520184#al-4. Accessed 10/22/2013.


See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.