Pseudohypoaldosteronism

Pseudohypoaldosteronism (PHA) is a condition that mimics hypoaldosteronism. However, the condition is due to a failure of response to aldosterone, and levels of aldosterone are actually elevated, due to a lack of feedback inhibition. Pseudohypoaldosteronism (PHA) is a condition that mimics hypoaldosteronism. However, the condition is due to a failure of response to aldosterone, and levels of aldosterone are actually elevated, due to a lack of feedback inhibition. This syndrome was first described by Cheek and Perry in 1958.Later pediatric endocrinologist Aaron Hanukoglu reported that there are two independent forms of PHA with different inheritance patterns: A renal form with autosomal dominant inheritance exhibiting salt loss mainly from the kidneys, and a multi-system form with autosomal recessive form exhibiting salt loss from kidney, lung, and sweat and salivary glands. The hereditary lack of responsiveness to aldosterone could be due to at least two possibilities: 1. A mutation in the mineralocorticoid receptor that binds aldosterone, or 2. A mutation in a gene that is regulated by aldosterone. Linkage analysis on patients suffering from the severe form of PHA excluded the possibility of linkage of the disease with the mineralocorticoid receptor gene region. Later, the severe form of PHA was discovered to be due to mutations in the genes SCNN1A, SCNN1B, and SCNN1G that code for the epithelial sodium channel subunits, α, β, and γ, respectively. A stop mutation in the SCNN1A gene has been shown to be associated with female infertility. Treatment of severe forms of PHA requires relatively large amounts of sodium chloride.These conditions also involve hyperkalemia.