SNP Shot: Genomic Insights

Pseudohypoaldosteronism type 2 (PHA2) is a condition characterized by disruptions in how the body manages sodium and potassium levels, electrolytes crucial for maintaining blood pressure. This regulation primarily occurs within the kidneys.

Individuals with PHA2 experience high blood pressure (hypertension) and elevated potassium levels in their blood (hyperkalemia), despite having normally functioning kidneys. The age at which PHA2 manifests varies significantly; diagnosis can occur from infancy through adulthood. Hyperkalemia is generally the first symptom, with hypertension developing later. Affected individuals also exhibit elevated chloride levels (hyperchloremia) and increased acidity (metabolic acidosis) in the blood – a combination termed hyperchloremic metabolic acidosis. These electrolyte imbalances can lead to nonspecific symptoms such as nausea, vomiting, fatigue, and muscle weakness. Furthermore, individuals with PHA2 may excrete high levels of calcium in their urine (hypercalciuria).

Inheritance:

PHA2 typically follows an autosomal dominant inheritance pattern. This means that possessing a single altered copy of a gene in each cell is enough to cause the condition. In most instances related to mutations in the WNK1, WNK4, or KLHL3 genes, the affected individual inherits the mutation from a parent who also has the condition. While some cases involving CUL3 gene mutations are inherited, many arise from new gene mutations in individuals with no prior family history of PHA2. In some instances involving the KLHL3 gene, inheritance follows an autosomal recessive pattern, requiring both copies of the gene in each cell to be mutated. In such cases, both parents carry one copy of the mutated gene, but usually do not exhibit any signs or symptoms of the condition themselves.