What are the genetic-familial varieties of primary aldosteronism?

Updated: Mar 24, 2020
  • Author: Gabriel I Uwaifo, MD; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
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Answer

Three distinct genetic-familial varieties of primary aldosteronism exist. Sutherland and colleagues first described the type 1 variety of familial primary aldosteronism, glucocorticoid-remediable aldosteronism (GRA), in 1966. In GRA, HTN responds clinically to small doses of glucocorticoids in addition to other antihypertensive agents. [2] The type 1 form of familial primary aldosteronism is due to an aberrantly formed chimeric gene product that combines the glucocorticoid-responsive (inhibitable) promoter of the 11beta-hydroxylase gene (CYP11B1) with the coding region of the aldosterone synthetase gene (CYP11B2). Under ambient glucocorticoid levels, the promoter is not fully transcriptionally silenced, and this leads to overexpression of aldosterone synthetase, with subsequent increased synthesis and secretion of aldosterone. (See Etiology and Workup.)

The type 2 variant of familial primary aldosteronism (which is not glucocorticoid sensitive) was first described in 1991. Although the exact genetic abnormality for type 2 primary aldosteronism has not been identified, data suggest that the locus for this disease is on band 7p22. [3]

The type 3 variant of familial primary aldosteronism is due to KCNJ5 (potassium inwardly rectifying channel, subfamily J, member 5) potassium channel mutations. This type was described by Lifton’s group in 2011. [4]


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