pseudohypoaldosteronism

Pseudohypoaldosteronism (PHA) is a group of rare inherited disorders characterized by resistance to the actions of aldosterone, leading to impaired sodium reabsorption and potassium excretion. In affected individuals, aldosterone levels are often elevated or inappropriately normal, but the kidney or other target tissues fail to respond properly, resulting in salt wasting, hyperkalemia, metabolic acidosis, and dehydration.

The condition is classified mainly into two genetic forms. Systemic pseudohypoaldosteronism type 1 is caused by mutations in the epithelial sodium channel (ENaC) subunits (SCNN1A, SCNN1B, SCNN1G) and is inherited in an autosomal recessive manner. This form affects multiple tissues that rely on ENaC function, including the kidney, colon, sweat glands, and lungs, and usually presents in infancy with severe salt wasting, dehydration, failure to thrive, and electrolyte disturbances. Renal pseudohypoaldosteronism type 1 results from mutations in the mineralocorticoid receptor gene NR3C2 and is typically inherited in an autosomal dominant pattern. This form mainly affects kidney responsiveness to aldosterone and often presents with a milder, more kidney-restricted clinical picture.

Clinical features overlap with other causes of salt-wasting, and diagnosis relies on the combination of laboratory findings and genetic testing. Laboratory signs include hyponatremia, hyperkalemia, metabolic acidosis, and elevated plasma renin activity with high aldosterone levels. Diagnosis is confirmed by identifying the causative gene mutation.

Management focuses on correcting and preventing electrolyte abnormalities and dehydration. Primary treatment is liberal salt supplementation and careful fluid management, particularly during illness or heat exposure. Hyperkalemia may require dietary adjustments or pharmacologic measures. Lifelong monitoring of growth, electrolyte status, and blood pressure is common, along with genetic counseling for affected families. Prognosis varies by form and severity, with systemic ENaC-related PHA often more challenging to manage in infancy.