Pseudohypoaldosteronism (PHA) is a collection of uncommon genetic or acquired conditions that disrupt the body’s capacity to retain salt and regulate potassium. This disorder arises from the kidneys’ diminished response to aldosterone, a hormone that normally helps maintain electrolyte balance. Individuals with PHA often exhibit high levels of aldosterone in their blood, yet their bodies do not respond to it effectively, leading to imbalances in sodium and potassium.
Understanding the Different Forms
Pseudohypoaldosteronism is broadly categorized into Type 1 (PHA1) and Type 2 (PHA2). PHA1 is characterized by the kidneys’ inability to respond to aldosterone, leading to excessive salt loss from the body. This resistance to aldosterone results in low sodium levels, high potassium levels, and elevated aldosterone in the blood.
Autosomal Dominant PHA1
PHA1 further divides into two main subtypes. Autosomal dominant PHA1, often referred to as renal PHA1, results from mutations in the NR3C2 gene, which codes for the mineralocorticoid receptor in the kidneys. This form is less severe and may improve as a child grows older, with salt loss primarily limited to the kidneys.
Autosomal Recessive PHA1
Conversely, autosomal recessive PHA1, also known as systemic PHA1, is caused by mutations in genes such as SCNN1A, SCNN1B, or SCNN1G. These genes are responsible for producing subunits of the epithelial sodium channel (ENaC), which is present in various organs beyond the kidneys, including the lungs, colon, and sweat glands. This systemic involvement leads to more severe symptoms that persist into adulthood.
PHA2
In contrast, PHA2, also known as Gordon Syndrome, presents with high potassium levels and metabolic acidosis but without salt wasting. This type is linked to mutations in WNK1 or WNK4 genes, which are involved in regulating kidney chloride transport. Unlike PHA1, individuals with PHA2 have low renin and aldosterone levels, and may experience hypertension.
Recognizing the Signs
The symptoms of pseudohypoaldosteronism vary depending on the specific type, with PHA1 manifesting in infancy due to significant salt loss. Infants with PHA1 may exhibit poor feeding, frequent vomiting, and signs of dehydration like lethargy. They might also fail to gain weight or grow as expected, a condition known as failure to thrive.
These symptoms arise because the body loses too much sodium, leading to low blood pressure and reduced blood volume. Infants may also display an unusual craving for salt, trying to compensate for the body’s sodium depletion. The electrolyte imbalance, specifically low sodium and high potassium, can contribute to weakness and fatigue.
For PHA2, symptoms appear later and are characterized by persistent high potassium levels and metabolic acidosis. Individuals may experience muscle weakness and heart rhythm abnormalities due to the elevated potassium. The body’s inability to excrete enough potassium and acid contributes to these manifestations.
Diagnosis and Treatment
Diagnosing pseudohypoaldosteronism involves a combination of laboratory tests and genetic analysis to pinpoint the specific type. Blood tests measure levels of sodium, potassium, aldosterone, and renin, providing a clear picture of electrolyte balance and hormonal activity. For instance, PHA1 is indicated by low sodium, high potassium, and high aldosterone and renin levels, despite the body’s resistance to aldosterone.
Urine tests also assess sodium excretion, which can confirm the extent of salt wasting, particularly in PHA1. Genetic testing then identifies specific gene mutations, such as those in NR3C2, SCNN1A, SCNN1B, or SCNN1G for PHA1, or WNK1 and WNK4 for PHA2, confirming the diagnosis.
Treatment strategies are tailored to the specific type of PHA and focus on managing electrolyte imbalances and preventing complications. For PHA1, salt supplementation is a primary intervention, often requiring significant amounts of sodium chloride to counteract the body’s salt loss and maintain adequate fluid volume. This helps to normalize sodium levels and alleviate dehydration.
Managing high potassium levels is also an aspect of treatment, which may involve dietary adjustments to restrict potassium intake or the use of potassium-lowering medications. For PHA2, diuretics, such as thiazide diuretics, are prescribed to help the kidneys excrete excess potassium and manage hypertension. Long-term management of pseudohypoaldosteronism involves regular monitoring of electrolyte levels and ongoing adjustments to treatment to ensure proper balance.