Familial hypercholesterolemia

Title

Not a rare disease

Summary Summary

Familial hypercholesterolemia is a condition characterized by very high levels of cholesterol in the blood due to mutations in the LDLR gene. People with hypercholesterolemia have a high risk of developing a form of heart disease called coronary artery disease, as well as health problems related to the buildup of excess cholesterol in other tissues (e.g., in the tendons and skin). Familial hypercholesterolemia tends to be passed through families in an autosomal dominant fashion. There are other hereditary forms of hypercholesterolemia caused by mutations in the APOB, LDLRAP1, or PCSK9 gene. However, most cases of high cholesterol are not caused by a single inherited condition, but result from a combination of lifestyle choices and the effects of variations in many genes.^[1]

Last updated: 6/18/2015

Symptoms Symptoms

Signs and symptoms in individuals with the autosomal dominant form of familial hypercholesterolemia (FH), also called the heterozygous form, may include:^[2]

Elevated total and LDL cholesterol levels
Coronary heart disease which can cause angina (heart pain), nonfatal or fatal heart attacks, need for angioplasty, or sudden death
Cerebrovascular disease which may cause stroke or transient ischemic attack (TIA)
Peripheral vascular disease which may cause pain when walking that is relieved by rest
Aortic aneurysm that may rupture, causing catastrophic bleeding and often death
Xanthomas (firm nodules under the skin caused by deposition of cholesterol on tendons)
Corneal arcus (an opaque, white line within the margin of the cornea that is above or surrounds the cornea)
Xanthelasmas (cholesterol deposits on, above or under the eyelids)

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.^[3]

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.^[3] 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.^[3]^[2]

Last updated: 10/22/2013

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Corneal arcus	-
Hypercholesterolemia	-
Xanthelasma	-

Last updated: 9/1/2016

Inheritance Inheritance

Familial hypercholesterolemia (FH) is usually inherited in an autosomal dominant manner (in which case it is referred to as heterozygous FH).^[3] 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.^[3]

Last updated: 10/22/2013

Treatment Treatment

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 statins, bile 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

Management Guidelines

The NORD Physician Guide for Familial hypercholesterolemia was developed as a free service of the National Organization for Rare Disorders (NORD) and it's medical advisors. The guides provide a resource for clinicians about specific rare disorders to facilitate diagnosis and treatment of their patients with this condition.

FDA-Approved Treatments

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

rosuvastatin (Brand name: Crestor) - Manufactured by iPR Pharmaceuticals, Inc.
FDA-approved indication: An adjunct to diet to reduce LDL-C, Total-C, nonHDL-C and ApoB in children and adolescents 7 to 17 years of age with homozygous familial hypercholesterolemia, either alone or with other lipid-lowering treatments (e.g., LDL apheresis).
National Library of Medicine Drug Information Portal
Medline Plus Health Information
Evolocumab (Brand name: Repatha) - Manufactured by Amgen Inc.
FDA-approved indication: As an adjunct to diet and other LDL-lowering therapies (e.g., statins, ezetimibe, LDL apheresis) in patients with HoFH who require additional lowering of LDL-C.
National Library of Medicine Drug Information Portal
Medline Plus Health Information

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

ClinicalTrials.gov lists trials that are studying or have studied Familial hypercholesterolemia. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.
The Research Portfolio Online Reporting Tool (RePORT) provides access to reports, data, and analyses of research activities at the National Institutes of Health (NIH), including information on NIH expenditures and the results of NIH-supported research. Although these projects may not conduct studies on humans, you may want to contact the investigators to learn more. To search for studies, enter the disease name in the "Text Search" box. Then click "Submit Query".

Organizations Organizations

Nonprofit support and advocacy groups bring together patients, families, medical professionals, and researchers. These groups often raise awareness, provide support, and develop patient-centered information. Many are the driving force behind research for better treatments and possible cures. They can direct people to research, resources, and services. Many groups also have experts who serve as medical advisors. Visit their website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD. Suggest an organization to add.

Organizations Supporting this Disease

American Heart Association
7272 Greenville Avenue
Dallas, TX 75231-4596
Toll-free: 800-242-8721
Telephone: 214-373-6300
Fax: 214-373-0268
E-mail: Review.personal.info@heart.org
Website: http://www.heart.org/
American Stroke Association
National Center
7272 Greenville Avenue
Dallas, TX 75231
Telephone: 888-478-7653
Website: http://www.strokeassociation.org/
Inherited High Cholesterol Foundation
University of Utah
Salt Lake City, UT 84108
Toll-free: 888-244-2465
Telephone: 801-581-8720
The FH Foundation
1515 Hope Street, Suite 204
South Pasadena, CA 91030
Telephone: 626-465-1234
E-mail: info@thefhfoundation.org
Website: http://www.thefhfoundation.org/

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Genetics Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by GeneTests, the American College of Medical Genetics, and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Financial Resources

Patient Access Network Foundation (PAN Foundation) has Assistance Programs for those with health insurance who reside in the United States. The disease fund status can change over time, so you may need to check back if funds are not currently available.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

Genetics Home Reference (GHR) contains information on Familial hypercholesterolemia. This website is maintained by the National Library of Medicine.
MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
The National Human Genome Research Institute's (NHGRI) website has an information page on this topic. NHGRI is part of the National Institutes of Health and supports research on the structure and function of the human genome and its role in health and disease.
The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Familial hypercholesterolemia. Click on the link to view a sample search on this topic.

Selected Full-Text Journal Articles

Gidding SS. Familial hypercholesterolemia: a decade of progress. J Pediatr. 2010 Feb;156(2):176-7.

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

Is familial hypercholesterolemia more common in certain populations? If so, how would this happen? See answer
How does diet affect the blood levels of LDL in people with familial hypercholesterolemia? See answer
I have been researching familial hypercholesterolemia. A couple of web sites have called it autosomal dominant. If I remember correctly that would mean that in order for a person to have FH, he would have to have a parent with FH. Is my thinking correct on this matter? See answer
What are the signs and symptoms of familial hypercholesterolemia? What genes cause this condition? See answer

References References

Hypercholesterolemia. Genetics Home Reference (GHR). 2007; http://ghr.nlm.nih.gov/condition=hypercholesterolemia. Accessed 10/22/2013.
Familial Hypercholesterolemia. NORD. July 25, 2011; http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/811/viewAbstract. Accessed 10/22/2013.
Learning About Familial Hypercholesterolemia. NHGRI. March 23, 2011; http://www.genome.gov/25520184. Accessed 10/22/2013.
Learning About Familial Hypercholesterolemia. NHGRI. March 23, 2011; http://www.genome.gov/25520184#al-4. Accessed 10/22/2013.