Autosomal recessive pseudohypoaldosteronism type I, including PHA1B1, is characterized by renal salt wasting and high concentrations of sodium in sweat, stool, and saliva. The disorder involves multiple organ systems and is especially threatening in the neonatal period. Laboratory evaluation shows hyponatremia, hyperkalemia, and increased plasma renin activity with high serum aldosterone concentrations. Respiratory tract infections are common in affected children and may be mistaken for cystic fibrosis (CF; 219700). Aggressive salt replacement and control of hyperkalemia results in survival, and the disorder appears to become less severe with age (review by Scheinman et al., 1999).
A milder, autosomal dominant form of type I pseudohypoaldosteronism (PHA1A; 177735) is caused by mutations in the mineralocorticoid receptor gene (MCR, NR3C2; 600983).
Gitelman syndrome (263800), another example of primary renal tubular salt wasting, is due to mutation in the thiazide-sensitive sodium-chloride cotransporter (SLC12A3; 600968).
Hanukoglu and Hanukoglu (2016) provided a detailed review of the ENaC gene family, including structure, function, tissue distribution, and associated inherited diseases. [from
OMIM]