Pseudohypoaldosteronism Type 1 due to a Novel Mutation in the Mineralocorticoid Receptor Gene

BACKGROUND/AIMS: Autosomal dominant pseudohypoaldosteronism type 1 is caused by mutations in the mineralocorticoid receptor (NR3C2) gene, often leading to life-threatening hyponatremia and hyperkalemia in the newborn period. We report a novel mutation in the NR3C2 gene, and report, for the first time, the association of well-treated pseudohypoaldosteronism with failure to thrive. This report additionally highlights the importance of aldosterone-sensitive sodium transport in the neonatal period. PATIENT AND METHODS: The patient presented with salt loss, hyperkalemia and a mild metabolic acidosis in the neonatal period (day of life 8). Further evaluation revealed significantly elevated levels of 18-hydroxycorticosterone, aldosterone and plasma renin activity, suggesting the diagnosis of pseudohypoaldosteronism. RESULTS: Analysis of the patient's NR3C2 gene revealed a novel missense mutation (c.1817G>C), which was subsequently analyzed in his parents and sister. Interestingly, the patient's mother was found to have an identical mutation. CONCLUSION: We report a novel mutation in the gene for the mineralocorticoid receptor and an unusual clinical course of pseudohypoaldosteronism type 1 in an adequately treated patient.