SNP Shot: Genomic Insights

Pseudohypoaldosteronism type 1 (PHA1) is a disorder affecting the body's ability to regulate sodium levels, a process crucial for maintaining proper blood pressure and fluid balance. While the kidneys primarily control sodium regulation, other tissues like sweat glands and the colon also play a role in sodium removal. The name PHA1 reflects its symptoms, which resemble (pseudo) a deficiency (hypo) of the hormone aldosterone, which normally regulates sodium. However, individuals with PHA1 actually have elevated aldosterone levels.

PHA1 is classified into two types based on severity, implicated genes, and inheritance patterns. Autosomal dominant PHA1 (also known as renal PHA1) primarily involves excessive sodium loss through the kidneys. This form is typically less severe and often improves during early childhood. Autosomal recessive PHA1 (also known as generalized or systemic PHA1), on the other hand, involves sodium loss from both the kidneys and other organs such as sweat glands, salivary glands, and the colon. This form is more severe and does not improve with age.

The earliest indications of both PHA1 types commonly include failure to thrive (poor weight gain and growth) and dehydration, usually observed in infancy. Key characteristics include excessive sodium excretion in the urine (salt wasting), leading to low blood sodium (hyponatremia) and high blood potassium (hyperkalemia). Infants with PHA1 may also develop high blood acidity (metabolic acidosis). Hyponatremia, hyperkalemia, or metabolic acidosis can manifest as nonspecific symptoms like nausea, vomiting, extreme fatigue, and muscle weakness.

Infants with autosomal recessive PHA1 may exhibit additional symptoms due to widespread organ involvement. They might experience irregular heartbeats (cardiac arrhythmia) or shock resulting from electrolyte imbalances. Furthermore, recurrent lung infections or skin lesions can occur. Although adults with autosomal recessive PHA1 may experience recurring episodes of salt wasting, they typically don't exhibit other signs or symptoms associated with the condition.

Inheritance:

PHA1 exhibits different inheritance patterns depending on the causative gene. PHA1 caused by mutations in the NR3C2 gene follows an autosomal dominant inheritance pattern. This means that inheriting only one copy of the mutated gene is sufficient to cause the disorder. Conversely, PHA1 caused by mutations in the SCNN1A, SCNN1B, or SCNN1G genes follows an autosomal recessive inheritance pattern. This requires inheriting two copies of the mutated gene, one from each parent. Parents of a child with an autosomal recessive condition each carry one copy of the mutated gene but usually do not display any symptoms of the disorder.