A case report of neonatal renal pseudohypoaldosteronism type I caused by a de novo variant in the NR3C2 gene

Pseudohypoaldosteronism type I (PHA I) is a rare hereditary disorder of mineralocorticoid resistance, with the renal form predominantly caused by NR3C2 variants. We report a male neonate presenting with severe hyperbilirubinaemia who was subsequently diagnosed with renal PHA I. Born at 38⁺⁶ weeks, he was admitted on day 7 for jaundice. Laboratory evaluation revealed refractory hyponatraemia, markedly elevated plasma aldosterone and renin levels, and ineffective conventional electrolyte therapy. Whole-exome sequencing identified a de novo heterozygous nonsense variant, c.1954C>T (p.Arg652*), in NR3C2, confirming the diagnosis. Aggressive sodium supplementation corrected the electrolyte imbalance, and follow-up showed normal growth and stable serum sodium. This case underscores the need to consider inherited renal tubulopathies in neonates with refractory hyponatraemia and highlights the pivotal role of genetic testing in precise diagnosis.