* Not a rare disease
What are the signs and symptoms of familial hypercholesterolemia?
How is familial hypercholesterolemia inherited?
How might familial hypercholesterolemia be treated?
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. 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. Treatment focuses on lowering LDL cholesterol levels in the blood and may include dietary modification and medication.
- 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.
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. 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.
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.
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.
- Learning About Familial Hypercholesterolemia. NHGRI. March 23, 2011; http://www.genome.gov/25520184. Accessed 10/22/2013.
- 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.
- 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#al-4. Accessed 10/22/2013.