Introduction
The condition known as pseudohypoaldosteronism type I (PHAI), which can be dominantly inherited, is characterized by kidney mineralocorticoid receptor alterations that are almost nonexistent. Since aldosterone's primary function is to stimulate the production of potassium and hydrogen, the disorder often manifests in the newborn period as hyperkalemia (increase in potassium), metabolic acidosis, and an elevated plasma aldosterone concentration.
Despite elevated amounts of aldosterone, this causes salt loss and hyperkalemia. It begins in childhood but becomes less severe as one ages. Additionally, there is a more severe recessive form of pseudohypoaldosteronism type I that is connected to mutations that cause epithelial sodium channels in the late distal tubules, the connecting tubule and collecting ducts, as well as other tissues expressing the epithelial sodium channels to lose their ability to function.
What Are the Types of Pseudohypoaldosteronism?
Pseudohypoaldosteronism comes in three different forms:
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Pseudohypoaldosteronism with autosomal recessive type I.
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Pseudohypoaldosteronism with autosomal dominant type I.
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Type II pseudohypoaldosteronism.
Either autosomal dominant or autosomal recessive inheritance occurs. With the exception of high aldosterone levels, pseudohypoaldosteronism type I is similar to other types of hypoaldosteronism.
Autosomal Recessive Pseudohypoaldosteronism Type I
It is also known as generalized or systemic pseudohypoaldosteronism type I and is characterized by salt loss from the kidneys and other organs such as the sweat glands, salivary glands, and colon. Pseudohypoaldosteronism type I of this form is more severe and does not get better with age.
The autosomal recessive variant typically has severe and long-lasting effects. Due to mutations that result in the diminished activity of the epithelial sodium channels on the luminal membrane of the collecting tubule (overactivity of epithelial sodium channels causes potassium excretion and sodium retention), infants are resistant to the effects of aldosterone. In tissues other than the kidneys, the sodium channel may be impacted, resulting in a military rash or consequences resembling those of cystic fibrosis.
Autosomal Dominant Pseudohypoaldosteronism Type I
It is also known as renal pseudohypoaldosteronism type I and is distinguished by excessive salt loss from the kidneys. This type of illness is typically moderate and gets better in early childhood. Mineralocorticoid resistance in children is caused by mutations in the mineralocorticoid receptor. As children get older, the autosomal dominant variant, which mostly affects the mineralocorticoid receptor in the kidney, may become less severe.
What Causes Pseudohypoaldosteronism Type I?
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Pseudohypoaldosteronism type I is an autosomal dominant or autosomal recessive condition that results from mutations in one of four separate sodium regulatory genes.
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Autosomal dominant pseudohypoaldosteronism type I is caused by mutations in the NR3C2 (nuclear receptor subfamily 3 group C member 2) gene.
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The mineralocorticoid receptor protein is made according to instructions from this gene.
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Pseudohypoaldosteronism type I is autosomal recessive when one of the SCNNIA (sodium channel epithelial I subunit alpha), SCNN IB (sodium channel epithelial I subunit beta), or SCNNIG (sodium channel epithelial I subunit gamma) genes is mutated. One of the components (subunits) of a protein complex known as the epithelial sodium channel is produced by each of these three genes (epithelial sodium channels).
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Specialized proteins in the cell membrane are controlled by the mineralocorticoid receptor, which governs sodium or potassium transport into cells.
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The mineralocorticoid receptor increases the amount and activity of these proteins at the cell membrane of specific kidney cells in response to indications that sodium levels are low, such as the presence of the hormone aldosterone.
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These proteins include epithelial sodium channels, which move sodium into cells, and another one that moves potassium and sodium into cells at the same time.
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These proteins aid in the removal of potassium from the body through secretion and aid in maintaining sodium levels in the body through reabsorption.
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When the NR3C2 gene is mutated, the mineralocorticoid receptor protein is either rendered inactive or performed improperly, making it unable to control the specialized proteins that transport sodium and potassium.
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Hyponatremia and hyperkalemia are the results of reduced potassium secretion and sodium reabsorption.
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Reduced or absent epithelial sodium channels channel function is the result of mutations in the SCNNIA, SCNNIB, and SCNNIG genes.
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Similar to autosomal dominant pseudohypoaldosteronism type I, hyponatremia and hyperkalemia are caused by reduced or absent epithelial sodium channel function in the kidneys.
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Lung infections and skin lesions are additional autosomal recessive pseudohypoaldosteronism type I indication and symptoms that are caused by non-functioning epithelial sodium channels in different bodily systems.
What Are the Signs and Symptoms Associated With Pseudohypoaldosteronism Type I?
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The failure to thrive (failure to acquire weight and grow at the expected rate).
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Dehydration is often observed in neonates.
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Excessive sodium loss in the urine (salt wasting) results in hyponatremia (low sodium levels in the blood).
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Excessive potassium levels in the blood (hyperkalemia).
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High levels of acid in the blood are also possible in children with (metabolic acidosis). Infants with pseudohypoaldosteronism type I may experience nonspecific symptoms such as nausea, vomiting, excessive weariness, and muscle weakness due to hyponatremia, hyperkalemia, or metabolic acidosis.
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Due to the involvement of several organs, infants with autosomal recessive pseudohypoaldosteronism type I may exhibit extra signs and symptoms. Because of the body's salt balance, those who are affected may occasionally endure episodes of an irregular heartbeat (cardiac arrhythmia) or shock.
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They might also experience recurrent skin lesions or lung infections.
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Adults with autosomal recessive pseudohypoaldosteronism type I can experience recurrent episodes of salt wasting, but they typically do not exhibit other disease-related symptoms.
What Are the Supportive Measures to Be Given in Patients Suffering From Pseudohypoaldosteronism Type I?
Patients with pseudohypoaldosteronism (PHA) experiencing hypovolemia and shock should be given the following supportive measures:
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Fluid resuscitation with isotonic sodium chloride solution at 20 milliliter per kilogram over 30 to 60 minutes. Repeated fluid infusions are possible until evidence of better organ perfusion is shown.
In order to protect the heart muscle and move potassium intracellularly until cation exchange resins begin to lower the serum potassium level, patients with severe hyperkalemia should be given the following supportive measures:
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Intravenous (IV) 10 percent calcium gluconate in doses of 0.5 to 1 milliliter per kilogram and sodium bicarbonate. In cases of severe hyperkalemia, an IV drip of 0.5 to 1 gram per kilogram glucose and 0.1 U per kilograms insulin over 30 minutes should also be taken into consideration. Pediatric nephrologists and endocrinologists should be consulted, too.
Conclusion
In pseudohypoaldosteronism type I, the body has trouble controlling its sodium levels. The kidneys are largely responsible for regulating sodium, which is crucial for maintaining fluid balance and blood pressure. But other organs, like the intestines and sweat glands, can also expel salt from the body. The condition known as pseudohypoaldosteronism type I gets its name from its signs and symptoms, which resemble (pseudo) low levels of the hormone aldosterone, which helps control sodium levels. On the other hand, aldosterone levels are high in those with pseudohypoaldosteronism type I. Supportive symptomatic treatment is the line of treatment for this condition.
