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Familial hyperaldosteronism is a condition in which the adrenal glands, which are small glands located on top of each kidney, produce excessive amounts of the hormone aldosterone. Aldosterone is sometimes called the salt-retaining hormone because it regulates the amount of salt retained by the kidneys. Excess aldosterone leads to increased retention of salt, which in turn increases the body's fluid levels and blood pressure. People with familial hyperaldosteronism may experience severe high blood pressure (hypertension), often early in life. Without treatment, hypertension increases the risk of strokes, heart attacks, and kidney failure.
Familial hyperaldosteronism is categorized into three types. Familial hyperaldosteronism type I, in which hypertension generally appears in childhood, can be treated with certain steroid medications called glucocorticoids, and so it is also known as glucocorticoid-remediable aldosteronism (GRA). In familial hyperaldosteronism type II, hypertension usually appears in early to middle adulthood and does not improve with glucocorticoid treatment. Familial hyperaldosteronism type III is characterized by enlargement of the adrenal glands to up to six times their normal size. Affected individuals experience childhood onset of severe hypertension that is difficult to treat and often results in damage to organs such as the heart and kidneys.
There are other forms of hyperaldosteronism that are not familial. These conditions may be caused by various problems in the adrenal glands or kidneys. In some cases, no cause can be found.
Familial hyperaldosteronism types I and III are rare disorders.The prevalence of familial hyperaldosteronism type II is unknown.
Familial hyperaldosteronism type I is caused by the abnormal fusion of two similar genes called CYP11B1 and CYP11B2, which are located close together on chromosome 8. These genes provide instructions for making two enzymes that are found in the adrenal glands.
The CYP11B1 gene provides instructions for making an enzyme called 11-beta-hydroxylase. This enzyme helps produce hormones called cortisol and corticosterone. The CYP11B2 gene provides instructions for making another enzyme called aldosterone synthase, which helps produce aldosterone.
In people with familial hyperaldosteronism type I, sections of the CYP11B1 gene and the CYP11B2 gene are abnormally fused together. The CYP11B1 section of the fused gene contains a regulatory region that normally starts the production of the 11-beta-hydroxylase enzyme. However, in the fused gene this regulatory region is attached to the section of the CYP11B2 gene that contains instructions for making the aldosterone synthase enzyme, so this enzyme is produced instead. The resulting overproduction of aldosterone synthase causes the adrenal glands to make too much aldosterone. An excess of this hormone leads to the signs and symptoms of familial hyperaldosteronism type I.
The regulatory region of the CYP11B1 gene is normally activated by a hormone called adrenocorticotrophic hormone (ACTH). The fused gene, because it includes the CYP11B1 regulatory region, is also activated by ACTH. Familial hyperaldosteronism type I responds to glucocorticoids because these medications lower ACTH levels, which reverses excessive aldosterone production and restores blood pressure levels to normal.
The genetic causes of familial hyperaldosteronism types II and III are unknown.
Changes in these genes are associated with familial hyperaldosteronism.
This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.
These resources address the diagnosis or management of familial hyperaldosteronism and may include treatment providers.
You might also find information on the diagnosis or management of familial hyperaldosteronism in Educational resources (http://www.ghr.nlm.nih.gov/condition/familial-hyperaldosteronism/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/familial-hyperaldosteronism/show/Patient+support).
General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).
To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.
You may find the following resources about familial hyperaldosteronism helpful. These materials are written for the general public.
You may also be interested in these resources, which are designed for healthcare professionals and researchers.
Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).
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