RESUMO
OBJECTIVE: To study patients with autosomal recessive pseudohypoaldosteronism type 1 and to relate pulmonary disease to gene mutations of the epithelial sodium channel (ENaC). STUDY DESIGN: Clinical and laboratory data were collected from 4 Swedish patients with pseudohypoaldosteronism type 1. The genes for ENaC and cystic fibrosis transmembrane conductance regulator were analyzed for mutations with methods including DNA sequencing. RESULTS: Three novel mutations were found in the alpha-gene of ENaC, 2 frameshifts (1449delC and 729delA) and 1 missense mutation resulting in the substitution of leucine for serine 562 in the alpha-chain (S562L). The 1449delC mutation was found in all patients in either homozygous or heterozygous form and seems to be the predominant cause of pseudohypoaldosteronism in Sweden. The allele coding for S562L also contained a transition converting tryptophan 493 to arginine (W493R), which seems to be a rare polymorphism. All patients had pulmonary symptoms to various degrees. The bacterial findings resembled, to some extent, those in cystic fibrosis, but development of chronic lung disease and progressive decline in lung function were not observed. CONCLUSIONS: Genetic deficiencies of the alpha subunit of the ENaC are associated with prominent lung symptoms, which are, however, clearly different from those in cystic fibrosis.