autosomal dominant pseudohypoaldosteronism type 1

Autosomal dominant pseudohypoaldosteronism type 1, also known as renal PHA1 or PHA1A, is a mild disorder characterized by primary mineralocorticoid resistance limited to the kidney. It is caused by pathogenic variants in the NR3C2 gene, which encodes the mineralocorticoid receptor important for aldosterone signaling. The condition typically presents in childhood and affects both males and females equally. Precise prevalence estimates are not well established, and severity can vary between individuals.

Individuals with autosomal dominant pseudohypoaldosteronism type 1 primarily experience disturbances in electrolyte balance. Hyperkalemia is consistently observed, while hyponatremia is reported in a subset of cases. These electrolyte abnormalities are often the initial signs that prompt further clinical evaluation. Not all individuals experience all features, and severity varies considerably, underscoring the variable nature of the condition.

The condition is caused by pathogenic variants in the NR3C2 gene, which plays a crucial role in encoding the mineralocorticoid receptor. This receptor is essential for mediating the effects of aldosterone, and its impaired function leads to resistance that manifests as electrolyte imbalances. Autosomal dominant inheritance means that a single altered copy of the gene is sufficient to cause the condition, and there is a 50% chance of passing the variant to offspring. However, due to variable expressivity and incomplete penetrance, not all individuals who carry the variant will exhibit the same symptoms.

Currently, management focuses on supportive care and symptom management. Because there are no targeted or approved treatments specifically for autosomal dominant pseudohypoaldosteronism type 1, treatment is individualized and aims at correcting electrolyte imbalances. Management strategies often involve dietary adjustments, careful monitoring of potassium and sodium levels, and other supportive measures as recommended by the healthcare team. Genetic counseling is also advised to help families understand the inheritance and implications for future family planning.

The overall outlook for individuals with autosomal dominant pseudohypoaldosteronism type 1 is generally favorable, given that the condition is mild and primarily affects kidney-specific functions. With current standards of care, many individuals manage their electrolyte imbalances effectively and maintain a good quality of life. Outcomes described in medical literature continue to evolve as standards of care improve, and variability in symptom severity means that the course can differ significantly between individuals. Families often find it helpful to connect with genetic counselors and expert healthcare providers to discuss treatment options and long-term management.

Clinical trials are underway exploring new treatment approaches for autosomal dominant pseudohypoaldosteronism type 1. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility.