Familial hyperaldosteronism types I and III (Familial hyperaldosteronism types I and III) - Genes CYP11B1, CYP11B2 and KCNJ5.
Hyperaldosteronism family is a group of inherited diseases in which the adrenal glands produce too much hormone aldosterone. Aldosterone helps control the amount of salt retained by the kidneys. Excess aldosterone causes the kidneys to retain more salt than normal, which in turn increases the levels of body fluids and blood pressure. People with familial hyperaldosteronism may develop severe hypertension, often early in life. Untreated hypertension increases the risk of strokes, heart attacks and kidney failure.
Family aldosteronism is classified into three types, which differ in their clinical characteristics and genetic causes. In type I familial hyperaldosteronism, hypertension usually occurs in childhood or adulthood and can range from mild to severe. This type can be treated with glucocorticoids, so also known as hyperaldosteronism treatable with glucocorticoids (GRA). In the familial hyperaldosteronism type II, hypertension usually occurs in early adulthood and does not improve with treatment with glucocorticoids. On the other hand, most individuals with familial hyperaldosteronism type III, adrenal glands extend up to six times its normal size. These individuals have severe hypertension that begins in childhood. Hypertension is difficult to treat and often causes heart and kidney damage. Rarely, people with type III have milder symptoms treatable hypertension without increasing the adrenal gland.
There are other ways that are unfamiliar aldosteronism. These forms are due to various problems in the adrenal glands or kidneys. In some cases, you can not detect increased aldosterone levels.
This process is due to mutations in the CYP11B1, CYP11B2 and KCNJ5 genes. Hyperaldosteronism family I is due to changes in CYP11B1 and CYP11B2 genes, while the type III familial hyperaldosteronism is due to changes in the KCNJ5 gene. The genetic cause for familial hyperaldosteronism type II is unknown.
The CYP11B1 gene, located on the long arm of chromosome 8 (8q21), encoding an enzyme called beta-hydroxylase 11. This enzyme helps produce cortisol and corticosterone. Specifically, the enzyme helps convert a molecule called 11-deoxycortisol to cortisol, and helps convert another molecule called 11-deoxycorticosterone to corticosterone. These processes are caused by the release of adrenocorticotropic hormone (ACTH) by the pituitary (hypophysis). Cortisol helps maintain blood glucose levels, which protects the body from physical stress and suppresses inflammation. Corticosterone becomes hormone aldosterone synthase enzyme aldosterone, encoded from CYP11B2 gene, located on the long arm of chromosome 8 (8q21-q22). Aldosterone helps control blood pressure by maintaining suitable concentrations of salt and fluid levels in the body. A genetic change that affects the CYP11B1 gene and CYP11B2 gene results in familial hyperaldosteronism type I. This change joins a section of the CYP11B1 gene called promoter region, which normally helps initiate encoding the enzyme 11-beta-hydroxylase, to section CYP11B2 gene encoding aldosterone synthase. When CYP11B1 CYP11B2 fuse and form anormals, too much aldosterone synthase occurs. This overproduction causes the adrenal glands to produce excess aldosterone, leading to signs and symptoms of type I disease.
The KCNJ5 gene, located on the long arm of chromosome 11 (11q24), encodes a protein that functions as a potassium channel, which means that transports potassium ions inside and outside of cells. In the adrenal glands, it is believed that the ion flow through potassium channels helps regulate aldosterone production. Aldosterone helps control blood pressure by maintaining the appropriate concentration of salt and fluid levels in the body. They have identified at least four mutations KCNJ5 gene in people with type III familial hyperaldosteronism. It is likely that mutations in the gene give rise to KCNJ5 production of potassium channels are less selective, allowing the passage of other ions, particularly sodium. As a result, the abnormal flow of ions in the activation of biochemical processes leading to increased aldosterone production, causing hypertension associated with type III familial hyperaldosteronism.
This disease is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient to express the disease.
Tests performed at IVAMI: at IVAMI we detect genetic alterations associated with types I and III familial hyperaldosteronism, by amplifying the CYP11B1 and CYP11B2 (type I) genes, followed by sequencing them to detect their fusion (chimeric gene), and KCNJ5 (type III), and its subsequent sequencing to detect mutations.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).