The prevalence of the autosomal dominant form of PHA1 is estimated to be approximately 1 in 80,000 newborns. The autosomal recessive form of PHA1 is much rarer, with only several hundred cases reported worldwide. PHA2 is extremely rare and its exact prevalence is unknown partly because its symptoms may be mild and it is likely underdiagnosed.

PHA is caused by different genetic mutations depending on the subtype. PHA1 is associated with resistance to aldosterone signalling. The more common autosomal dominant renal form is caused by mutations in the NR3C2 gene which encodes the minerocorticoid receptor that binds aldosterone. The autosomal recessive form of PHA1 is caused by mutations in the SCNN1A, SCNN1B or SCNN1G genes that encode pieces (subunits) of the epithelial sodium channel ENaCl, affecting the kidney, lung, sweat glands, colon and salivary glands. PHA2 is caused by mutations in genes such as WNK1, WNK4, KLHL3 or CUL3, which regulate sodium and potassium transport in the kidneys.

Symptoms typically appear in infancy for PHA1, while PHA2 may be diagnosed later in life.

Common symptoms for PHA1:

• Dehydration

• Vomiting and poor feeding

• Failure to thrive (lethargy, poor weight gain)

• Salt craving

• Hyponatremia (low sodium)

• Metabolic acidosis (imbalance in body’s acid-base balance)

• Hyperkalemia (high potassium levels)

• Muscle weakness (due to high potassium)

• In the systemic autosomal recessive form, patients may have recurrent chest infections or skin rashes.

Common symptoms for PHA2:

• High blood pressure (hypertension)

• Hyperkalemia (high potassium levels)

• Growth delays in some children

• Hypervolemia (excess fluid in bloodstream)

Diagnosis is based on a combination of clinical presentation, laboratory findings and genetic testing.

Typical findings for PHA1 include:

• Elevated aldosterone

• Elevated renin, a blood pressure regulator

• Hyponatremia (low sodium in blood)

• High sodium levels in urine

• Hyperkalemia

• Metabolic acidosis

• Normal or elevated cortisol

In PHA2:

• Hyperkalemia

• Hypertension

• Suppressed renin

• Normal or mildly elevated aldosterone

Genetic confirmation:

• The PHA1 renal autosomal dominant form is confirmed by mutations in the NR3C2 gene (mineralocorticoid receptor); the systemic recessive form is confirmed by loss-of-function mutations in ENaC subunit genes (SCNN1A, SCNN1B, SCNN1G).

The diagnosis of PHA2 is established by identification of mutations in CUL3, WNK1, WNK4 or KLHL3.

Treatment focuses on correcting electrolyte imbalances.

PHA1:

• High dose oral sodium chloride supplements

• Potassium-lowering treatments

• Intravenous fluids during crises

• Sodium bicarbonate to manage metabolic acidosis

• Systemic PHA1 often requires long-term aggressive salt replacement

PHA2:

• Low salt diet

• Thiazide diuretic drugs to lower blood pressure and potassium levels

PHA prognosis varies by subtype.

For renal autosomal dominant PHA1, the prognosis is generally excellent as resistance to aldosterone often improves as a child grows older, and many can eventually stop salt supplements. In contrast, the systemic autosomal recessive form of PHA1 is a lifelong severe condition that requires strict adherence to treatment and monitoring to prevent life-threatening electrolyte crises. For PHA2, the prognosis is good and life expectancy is normal with lifelong therapy to manage blood pressure and potassium levels.

1. Amir Babiker, et al. 2024. “Pseudohypoaldosteronism: A challenging diagnosis with management pitfalls - Case series.” Journal of Clinical and Translational Endocrinology: Case Reports. 32: 100172. https://doi.org/10.1016/j.jecr.2024.100172.

2. Diaz-Thomas A. Pseudohypoaldosteronism. Medscape/eMedicine. Updated August 15, 2025. https://emedicine.medscape.com/article/924100-overview.

3. NIH Genetic and Rare Diseases Information Center (GARD): Pseudohypoaldosteronism type 1.

4. Orphanet. Pseudohypoaldosteronism type 1. September 2021. https://www.orpha.net/en/disease/detail/756.

5. Orphanet. Pseudohypoaldosteronism type 2. May 2019. https://www.orpha.net/en/disease/detail/757.