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Familial Hypercholesterolemia

National Organization for Rare Disorders, Inc.


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.


  • autosomal dominant hypercholesterolemia

Disorder Subdivisions

  • LDL receptor disorder
  • familial ligand-defective apolipoprotein B
  • PCSK9
  • heterozygous familial hypercholesterolemia
  • homozygous familial hypercholesterolemia

General Discussion


Familial hypercholesterolemia (FH) is characterized by very high levels of total and low-density lipoprotein (LDL) cholesterol, often called the "bad" cholesterol. The levels of another blood lipid, triglycerides, are usually normal and the levels of high-density lipoprotein (HDL) cholesterol (the "good" cholesterol) are typically low or normal. The condition greatly increases the risk of atherosclerosis (hardening of the arteries), which causes heart attacks, strokes and other serious vascular conditions. Untreated men with FH often develop symptoms of coronary heart disease (CHD) in their early forties and women, in their early fifties. If one or more other major risk factors for CHD are present, especially cigarette smoking and diabetes mellitus, the risk of developing symptomatic CHD is greatly increased. Women without other major risk factors for CHD may survive to old age without developing symptomatic disease. The current National Cholesterol Education Program Adult Treatment Panel III defines major CHD risk factors as cigarette smoking, high blood pressure, age (men 45 or older; women 55 or older), family history of premature CHD in parents or siblings (men before age 55; women before age 65) and HDL cholesterol below 40 mg/dL. Patients with diabetes are currently considered to have a risk for a heart attack (fatal or nonfatal) as great as those who have already had a heart attack.


In 1973, Joseph Goldstein and Michael Brown identified and characterized a cell membrane protein they called the LDL receptor and the mutations in the gene that interfered with its function. A normally functioning receptor lowers the blood levels of LDL cholesterol by taking up the particles (lipoproteins) that carry the bad cholesterol. A mutation in one of the genes caused a decrease either in the number or function of the receptors, resulting in the extreme LDL cholesterol elevations of 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. Since that time, other genes have been identified that cause severe hypercholesterolemia.

Almost all genes have two copies, one inherited from each parent's chromosome. A dominant mutation is expressed if only one copy is present. A recessive mutation must be present in both chromosomes. FH patients who carry a single mutation have heterozygous FH and those with a mutation on both chromosomes have homozygous FH.


American Heart Association

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Dallas, TX 75231

Tel: (214)784-7212

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NIH/National Heart, Lung and Blood Institute

P.O. Box 30105

Bethesda, MD 20892-0105

Tel: (301)592-8573

Fax: (301)251-1223



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


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 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 or email

Last Updated:  7/25/2011

Copyright  1991, 1995, 1996, 1998, 2006, 2011 National Organization for Rare Disorders, Inc.

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