Mineralocorticoid resistance

Abstract

Mineralocorticoid resistance, also known as type I pseudohypoaldosteronism (PHA1), is a rare inherited disease characterized by salt wasting, dehydration and failure to thrive in the newborn. Two different forms of the disease, which present with either systemic or exclusively renal resistance to aldosterone, are associated with two different modes of inheritance. The generalized, recessive form of the disease is due to abnormalities in the epithelial sodium channel, and inactivating mutations of the mineralocorticoid receptor are responsible for the autosomal dominant form of PHA1 and some sporadic cases. Here, we review the role of aldosterone in the maintenance of normal sodium balance and discuss the different forms of mineralocorticoid resistance and the underlying genetic abnormalities. Although important progress has been made in the past years, there remain several families in whom the genetic defect has not been identified. Precise clinical diagnosis and establishment of intermediate phenotypes should be helpful for identifying other genes involved in PHA1 and gaining new insight into the regulation of sodium homeostasis.