A novel mutation in the human mineralocorticoid receptor gene in a Japanese family with autosomaldominant pseudohypoaldosteronism type 1

[Introduction] Pseudohypoaldosteronism type 1 (PHA1) is a rare disease that manifests in infancy with hyponatremia, hyperkalemia, and metabolic acidosis, regardless of renin-angiotensin system (RAS) hyperactivity. PHA1 has autosomal recessive systemic and autosomal dominant renal forms. The systemic form of PHA1 is characterized by severe resistance to aldosterone in multiple organs, including the kidney, colon, sweat and salivary glands, and lung. Patients with renal PHA1 are treated with supplemental oral salt, and they typically show gradual clinical improvement with regard to renal salt loss during childhood. Usually, sodium supplementation becomes unnecessary at one to three years of age. Systemic PHA1 is caused by mutations in the amiloride-sensitive luminal sodium channel (ENaC) gene, the protein product of which is responsible for sodium reabsorption. In contrast, in the renal PHA1 form, aldosterone resistance is present only in the kidney. Renal PHA1 results in renal salt loss and failure to thrive during infancy.