Which are the causes of Hypokalemic periodic paralysis?

Causes of Hypokalemic Periodic Paralysis

Hypokalemic periodic paralysis (HPP) is a rare genetic disorder characterized by episodes of muscle weakness or paralysis. It is primarily caused by abnormalities in the functioning of ion channels in muscle cells, leading to imbalances in potassium levels. These imbalances can trigger the onset of paralysis. While the exact mechanisms underlying HPP are not fully understood, several factors have been identified as potential causes or triggers for the condition.

Genetic Mutations

Genetic mutations play a crucial role in the development of HPP. The majority of HPP cases are inherited in an autosomal dominant pattern, meaning that a single copy of the mutated gene from one parent is sufficient to cause the disorder. Mutations in genes encoding ion channels, particularly the skeletal muscle calcium channel (CACNA1S) and the sodium channel (SCN4A), have been identified as the primary genetic causes of HPP. These mutations disrupt the normal functioning of ion channels, leading to abnormal muscle cell excitability and potassium imbalances.

Triggers and Precipitating Factors

HPP episodes can be triggered or exacerbated by various factors, including:

• Fasting or high-carbohydrate meals: Skipping meals or consuming excessive carbohydrates can lead to insulin release, which in turn promotes cellular uptake of potassium, potentially triggering an episode of paralysis.


• High-sodium intake: Consuming foods high in sodium can increase the excretion of potassium in the urine, leading to a decrease in potassium levels and the onset of paralysis.


• Strenuous exercise: Intense physical activity can cause potassium to shift from the bloodstream into muscle cells, resulting in a decrease in serum potassium levels and subsequent paralysis.


• Emotional stress: Stressful situations or emotional distress can trigger the release of stress hormones, such as adrenaline, which can disrupt potassium balance and precipitate an episode.


• Certain medications: Some medications, such as beta-agonists, diuretics, and corticosteroids, can affect potassium levels and potentially trigger HPP episodes.

Hormonal Factors

Hormonal factors can also contribute to the development of HPP. Fluctuations in hormone levels, particularly during puberty, menstruation, or pregnancy, have been associated with an increased frequency of paralysis episodes. The exact mechanisms by which hormones influence HPP are not fully understood, but it is believed that hormonal changes may affect ion channel activity and potassium balance in muscle cells.

Other Factors

While less common, there are additional factors that may contribute to the development or exacerbation of HPP:

• Cold temperatures: Exposure to cold temperatures has been reported to trigger paralysis episodes in some individuals with HPP. Cold temperatures may alter ion channel function and impair muscle cell excitability.


• Alcohol consumption: Excessive alcohol intake can disrupt potassium balance and trigger episodes of muscle weakness or paralysis in susceptible individuals.


• Acid-base imbalances: Disturbances in the body's acid-base balance, such as metabolic alkalosis or acidosis, can affect potassium levels and potentially precipitate HPP episodes.

It is important to note that the severity and frequency of HPP episodes can vary widely among individuals, even within the same family. The specific combination of genetic, environmental, and physiological factors likely contributes to the unique presentation of HPP in each affected individual.