Genetic disorders affecting aldosterone synthesis and action

Genetic defects in aldosterone biosynthesis and action affect blood pressure and electrolyte homeostasis. Aldosterone synthase deficiency, salt-wasting forms of congenital adrenal hyperplasia, and adrenal hypoplasia congenita cause aldosterone deficiency, signs of which include hyponatremia, hyperkalemia, hypovolemia, elevated plasma renin activity, and sometimes shock. End-organ unresponsiveness to aldosterone (pseudohypoaldosteronism) has a similar phenotype. Conversely, the inappropriate regulation of aldosterone synthesis seen in glucocorticoid-suppressible hyperaldosteronism may cause hypokalemia, suppressed plasma renin activity, and hypertension. Similar problems occur when the normal ligand specificity of the aldosterone receptor is lost, as occurs in the syndrome of apparent mineralocorticoid excess due to 11β-hydroxysteroid dehydrogenase deficiency. With the exception of pseudohypoaldosteronism, all of the genes involved in these disorders have recently been cloned and mutations causing each disease have been identified.