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    Familial Hypercholesterolemia

    Important
    It is possible that the main title of the report Familial Hypercholesterolemia is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

    Synonyms

    • FH
    • autosomal dominant hypercholesterolemia
    • hyperlipoproteinemia, type IIA
    • APOB-related familial hypercholesterolemia, autosomal dominant
    • LDLR-related familial hypercholesterolemia, autosomal dominant
    • PCSK9-related familial hypercholesterolemia, autosomal dominant

    Disorder Subdivisions

    • None

    General Discussion

    Summary
    Familial hypercholesterolemia (FH) is a diagnosis which refers to individuals with very significantly elevated low-density lipoprotein (LDL) cholesterol (LDL-C) or "bad cholesterol". In heterozygous familial hypercholesterolemia (HeFH), an individual inherits a mutation (alteration) for FH from one (affected) parent. In homozygous familial hypercholesterolemia (HoFH), an individual inherits a causal FH mutation from both parents. For the purposes of this report, "FH" will refer to HeFH unless otherwise stated.
    FH is one of the most common genetic diseases and affects at least 1 in 500 individuals. This may be an underestimate as recent genetic studies indicate that FH may be as common as 1 in 250 in European Caucasian populations. If DNA testing is performed, most (60-80%) will be found to have a mutation in one of three relevant genes. Others may express these clinical findings for other reasons or may carry a mutation in a gene or genes that have yet to be discovered.

    FH is characterized by very high levels of LDL-C, as well as of total cholesterol. The condition greatly increases the risk of hardening of the arteries (atherosclerosis), which can lead to heart attacks, strokes and other vascular conditions. Individuals with FH have a 20-fold increased risk for coronary heart disease (CHD). Untreated men have a 50% risk of a nonfatal or fatal coronary event by age 50 years; untreated women have a 30% risk by age 60 years. If one or more other risk factors for CHD are present, especially cigarette smoking or diabetes mellitus, the risk of developing symptomatic CHD is even higher.

    FH is treatable and the associated cardiovascular disease is largely preventable with early and intensive treatment, using statins, additional drugs, and other means. Family members of an affected individual found through "cascade screening" or "family tracing" who have not yet exhibited symptoms and who are appropriately treated are likely to live a normal lifespan.

    HoFH is very rare (~ 1 in 250,000 to 1 in 1 million). LDL-C levels are usually, though not always, > 400 mg/dl. Severe vascular disease including CHD and aortic stenosis are often seen by the teenage years. Without very aggressive treatment including LDL-C apheresis and HoFH specific medications, mortality is common before age 30.

    Introduction

    In 1973, Joseph Goldstein and Michael Brown identified and characterized a cell membrane protein they called the LDL receptor and the mutations in the low-density lipoprotein receptor gene (LDLR) that interfered with its function. Normally functioning receptors lower the blood levels of LDL-C by taking up the lipoproteins that carry LDL-C in the liver. Mutations in this gene cause a decrease either in the number or function of the receptors, resulting in the extreme LDL-C elevations seen in FH. Goldstein and Brown became the first investigators to identify a mutation that caused a metabolic disorder when only a single abnormal gene was present. In 1985 they won the Nobel Prize in Medicine for this work. Their pioneering work and the subsequent studies of LDL-C metabolism in FH patients greatly contributed to our knowledge about the link between cholesterol and heart disease and led to the development of numerous therapeutic agents that benefit a very large number of individuals with high cholesterol. Since that time, other genes causing FH such as the apolipoprotein B-100 gene (APOB) and the proprotein convertase subtilisin/kexin type 9 gene (PCSK9) have been identified (see below).

    Importantly, there is a great deal of evidence showing that early diagnosis and intensive treatment can prevent illness and death due to FH.

    Resources

    American Heart Association
    7272 Greenville Avenue
    Dallas, TX 75231
    Tel: (214)784-7212
    Fax: (214)784-1307
    Tel: (800)242-8721
    Email: Review.personal.info@heart.org
    Internet: http://www.heart.org

    NIH/National Heart, Lung and Blood Institute
    P.O. Box 30105
    Bethesda, MD 20892-0105
    Tel: (301)592-8573
    Fax: (301)251-1223
    Email: nhlbiinfo@rover.nhlbi.nih.gov
    Internet: http://www.nhlbi.nih.gov/

    Genetic and Rare Diseases (GARD) Information Center
    PO Box 8126
    Gaithersburg, MD 20898-8126
    Tel: (301)251-4925
    Fax: (301)251-4911
    Tel: (888)205-2311
    TDD: (888)205-3223
    Internet: http://rarediseases.info.nih.gov/GARD/

    International FH Foundation
    St. Andrews Court
    Wellington St.
    Thame
    Oxfordshire, OX9 3WT
    Tel: 01235 531 203
    Email: ask@fh-foundation.org
    Internet: http://www.fh-foundation.org

    FH Foundation
    1515 Hope Street
    Suite 204
    South Pasandena, CA 91030
    Tel: (626)465-1234
    Fax: (626)628-2146
    Email: info@theFHfoundation.org
    Internet: http://www.thefhfoundation.org

    For a Complete Report:

    This is an abstract of a report from the National Organization for Rare Disorders (NORD). A copy of the complete report can be downloaded free from the NORD website for registered users. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational therapies (if available), and references from medical literature. For a full-text version of this topic, go to www.rarediseases.org and click on Rare Disease Database under "Rare Disease Information".

    The information provided in this report is not intended for diagnostic purposes. It is provided for informational purposes only. NORD recommends that affected individuals seek the advice or counsel of their own personal physicians.

    It is possible that the title of this topic is not the name you selected. Please check the Synonyms listing to find the alternate name(s) and Disorder Subdivision(s) covered by this report

    This disease entry is based upon medical information available through the date at the end of the topic. Since NORD's resources are limited, it is not possible to keep every entry in the Rare Disease Database completely current and accurate. Please check with the agencies listed in the Resources section for the most current information about this disorder.

    For additional information and assistance about rare disorders, please contact the National Organization for Rare Disorders at P.O. Box 1968, Danbury, CT 06813-1968; phone (203) 744-0100; web site www.rarediseases.org or email orphan@rarediseases.org

    Last Updated: 7/4/2014
    Copyright 1991, 1995, 1996, 1998, 2006, 2011, 2014 National Organization for Rare Disorders, Inc.

    WebMD Medical Reference from the National Organization for Rare Disorders

    Last Updated: May 28, 2015
    This information is not intended to replace the advice of a doctor. Healthwise disclaims any liability for the decisions you make based on this information.

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    Your total cholesterol level is Borderline High, but fortunately your level of "bad" LDL cholesterol is optimal. This could mean you have a high level of high-density lipoprotein, or "good" HDL cholesterol, which protects against heart disease. Or you could have other non-measured increases in LDL-like particles that can increase heart disease. Your LDL level also could be optimal if you are taking a statin medication. Please check with your doctor to get your complete lipid profile and see if you may need additional treatment. In the meantime, find more information on WebMD's Cholesterol Health Center.

    Your total cholesterol level is Borderline High, but fortunately your level of "bad" LDL cholesterol is near optimal. This could mean you have a high level of high-density lipoprotein, or "good" HDL cholesterol, which protects against heart disease. Or you could have other non-measured increases in LDL-like particles that can increase heart disease. Your LDL level also could be optimal if you are taking a statin medication. Please check with your doctor to get your complete lipid profile and see if you may need additional treatment. In the meantime, find more information on WebMD's Cholesterol Health Center.

    Your total cholesterol level is Borderline High. Your level of "bad" LDL cholesterol is Borderline High, too. Working to bring down your total cholesterol decreases your LDL cholesterol level. You can do this by exercising more and eating less food with saturated fats. Check food labels!

    Your total cholesterol level is Borderline High. Your level of "bad" LDL cholesterol is High. Working to bring down your total cholesterol decreases your LDL cholesterol level. You can do this by exercising more and eating less food with saturated fats. Check food labels!

    Your total cholesterol level is Borderline High. But your level of "bad" LDL cholesterol is Very High. Working to bring down your total cholesterol decreases your LDL cholesterol level. You can do this by exercising more and eating less food with saturated fats. Check food labels!

    Your total cholesterol is High, but your level of "bad" LDL cholesterol is optimal. This could mean you have a high level of high-density lipoprotein, or "good" HDL cholesterol, which protects against heart disease. Or you could have elevated secondary lipids, such as non-HDL particles that increase the risk of heart disease. Your LDL level also could be optimal if you are taking a statin medication. Please check with your doctor to get your complete lipid profile and see if you may need additional treatment. In the meantime, find more information on WebMD's Cholesterol Health Center.

    Your total cholesterol is High, but your level of "bad" LDL cholesterol is near optimal. This could mean you have a high level of high-density lipoprotein, or "good" HDL cholesterol, which protects against heart disease. Or you could have elevated secondary lipids, such as non-HDL particles that increase the risk of heart disease. Your LDL level also could be optimal if you are taking a statin medication. Please check with your doctor to get your complete lipid profile and see if you may need additional treatment. In the meantime, find more information on WebMD's Cholesterol Health Center.

    Your total cholesterol level is High. Your level of "bad" LDL cholesterol is Borderline High. Working to bring down your total cholesterol decreases your LDL cholesterol level. You can do this by exercising more and eating less food with saturated fats. Check food labels!

    Your total cholesterol level is High. Your level of "bad" LDL cholesterol is High, too. Working to bring down your total cholesterol decreases your LDL cholesterol level. You can do this by exercising more and eating less food with saturated fats. Check food labels! If you are struggling to bring down your total cholesterol and LDL cholesterol levels, your doctor may prescribe medication, such as statins. Following medication, dietary, and exercise instructions should result in improvements.

    Your total cholesterol level is High, and your level of "bad" LDL cholesterol is Very High. Working to bring down your total cholesterol decreases your LDL cholesterol level. You can do this by exercising more and eating less food with saturated fats. Check food labels! If you are struggling to bring down your total cholesterol and LDL cholesterol levels, your doctor may prescribe statins or other cholesterol-lowering medications.

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