A novel NR3C2 mutation in a Japanese patient with the renal form of pseudohypoaldosteronism type 1

Pseudohypoaldosteronism type 1 (PHA1) is a rare disease characterized by congenital resistance to the action of aldosterone on epithelial tissue; PHA1 results in excessive salt wasting despite very high plasma aldosterone and renin levels (1–3). There are 3 types of PHA1. The systemic form of PHA1 is inherited in an autosomal recessive manner and manifests as severe life-long salt wasting caused by mineralocorticoid resistance in multiple target tissues (e.g., sweat glands, salivary glands, colonic epithelium, and lung). The renal form of PHA1 (adPHA1) is inherited in an autosomal dominant manner. In this form, mineralocorticoid resistance exists only in the kidney; moreover, salt wasting and other symptoms improve around 1–3 yr of age (1–3). The third type of PHA1 is the transient form, which is commonly seen in patients with urinary tract infection or obstructive uropathy. In the transient form, clinical symptoms disappear after treatment. adPHA1 is caused by a heterozygous mutation in NR3C2, which encodes the mineralocorticoid receptor (MR). Herein, we report the case of a young girl with adPHA1, a novel mutation in NR3C2, hyponatremia, and failure to thrive associated with urinary tract infection. We also describe a genetic analysis of her family.