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Pseudohypoaldosteronism type 2 (PHA2) is a condition characterized by problems regulating the amount of sodium and potassium in the body. Sodium and potassium are important in the control of blood pressure, and their regulation occurs primarily in the kidneys.
People with PHA2 have high blood pressure (hypertension) and high levels of potassium in their blood (hyperkalemia) despite having normal kidney function (normal glomerular filtration rate). The age of onset of the condition is variable and difficult to pinpoint; some affected individuals are diagnosed in infancy or childhood, and others are diagnosed in adulthood. Hyperkalemia usually occurs first, and hypertension develops later in life. Affected individuals may also have high levels of chloride (hyperchloremia) or acid (metabolic acidosis) in their blood. People with hyperkalemia, hyperchloremia, and metabolic acidosis can have nonspecific symptoms like nausea, vomiting, extreme tiredness (fatigue), and muscle weakness.
PHA2 is a rare condition; however, the prevalence is unknown.
Mutations in either of two related genes, WNK1 and WNK4, can cause PHA2. These genes play a role in regulating blood pressure by helping to control the amount of sodium and potassium in the body. The proteins produced from the WNK1 and WNK4 genes act as kinases, which are enzymes that change the activity of other proteins by adding a cluster of oxygen and phosphorus atoms (a phosphate group) at specific positions.
The WNK1 and WNK4 proteins regulate channels in the cell membrane that control the transport of sodium or potassium into and out of cells, which occurs primarily in the kidneys. Sodium channels help transport sodium into specialized cells of the kidney, from which it is transferred to the blood. This transfer helps keep sodium in the body through a process called reabsorption. Potassium channels handle excess potassium that has been transferred from the blood into the kidney cells. The channels transport the potassium out of the cells in a process called secretion, so that it can be removed from the body in the urine.
The WNK4 protein normally blocks (inhibits) sodium and potassium channels, which decreases sodium reabsorption and potassium secretion. The WNK1 protein normally stops WNK4's inhibition of sodium channels, which increases sodium reabsorption. The WNK1 protein also inhibits potassium channels, which decreases potassium secretion.
Mutations in the WNK1 gene increase the activity of the gene and lead to excess WNK1 protein. The excess protein abnormally increases sodium reabsorption and blocks potassium secretion. These effects lead to increased sodium and potassium levels in the body, causing hypertension and hyperkalemia.
Mutations in the WNK4 gene lead to an abnormal protein that no longer inhibits sodium channels but inhibits potassium channels more strongly. Like WNK1 gene mutations, mutations in the WNK4 gene lead to increased sodium reabsorption and decreased potassium secretion, resulting in hypertension and hyperkalemia.
Changes in these genes are associated with pseudohypoaldosteronism type 2.
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.
In most cases, an affected person has one parent with the condition.
These resources address the diagnosis or management of pseudohypoaldosteronism type 2 and may include treatment providers.
You might also find information on the diagnosis or management of pseudohypoaldosteronism type 2 in Educational resources and 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.
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 pseudohypoaldosteronism type 2 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.
For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
Ask the Genetic and Rare Diseases Information Center (https://rarediseases.info.nih.gov/gard).
acidosis ; autosomal ; autosomal dominant ; cell ; cell membrane ; chloride ; familial ; gene ; hyperkalemia ; hyperpotassemia ; hypertension ; inherited ; kidney ; oxygen ; phosphate ; phosphorus ; potassium ; prevalence ; protein ; secretion ; sodium ; syndrome
You may find definitions for these and many other terms in the Genetics Home Reference Glossary.
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