BACKGROUND/AIMS: Pseudohypoaldosteronism Type 1 (PHA1) is a rare heterogeneous syndrome characterized by severe salt loss, hyperkalemia, hyponatremia, metabolic acidosis, hyperaldosteronism and hyperreninemia. Multi-system form of PHA1 is caused by mutations in one of the genes encoding the α, β and γ subunits of epithelial sodium channels (ENaC). In this study, we presented a novel splice site mutation in the beta-gene of ENaC in a patient with multi-system PHA. METHODS: We performed DNA sequencing analysis of SCNN1A, SCNN1B, SCNN1G and NR3C2 genes. RESULTS: We found a novel c.1266-1G>C homozygous splice site mutation in intron 8 of the SCNN1B gene. Initially elevated plasma renin activity (PRA) and aldosterone levels of the patient returned to normal with large amounts of dietary salt and serum sodium (Na+) and potassium (K+) levels were within normal range at the end of the first year of life. CONCLUSION: This improvement may be due to partial activity of mutated ENaC subunits, reduced dependence on aldosterone in salt homeostasis with increasing age, and alternative regulating mechanisms in sodium homeostasis. The results enhance our understanding of the pathophysiology of this disorder and the mechanisms of renal salt conservation.
BACKGROUND/AIMS: Pseudohypoaldosteronism Type 1 (PHA1) is a rare heterogeneous syndrome characterized by severe salt loss, hyperkalemia, hyponatremia, metabolic acidosis, hyperaldosteronism and hyperreninemia. Multi-system form of PHA1 is caused by mutations in one of the genes encoding the α, β and γ subunits of epithelial sodium channels (ENaC). In this study, we presented a novel splice site mutation in the beta-gene of ENaC in a patient with multi-system PHA. METHODS: We performed DNA sequencing analysis of SCNN1A, SCNN1B, SCNN1G and NR3C2 genes. RESULTS: We found a novel c.1266-1G>C homozygous splice site mutation in intron 8 of the SCNN1B gene. Initially elevated plasma renin activity (PRA) and aldosterone levels of the patient returned to normal with large amounts of dietary salt and serum sodium (Na+) and potassium (K+) levels were within normal range at the end of the first year of life. CONCLUSION: This improvement may be due to partial activity of mutated ENaC subunits, reduced dependence on aldosterone in salt homeostasis with increasing age, and alternative regulating mechanisms in sodium homeostasis. The results enhance our understanding of the pathophysiology of this disorder and the mechanisms of renal salt conservation.