Hypokalemic periodic paralysis (HypoKPP) is characterized by episodes of extreme muscle weakness or paralysis associated with a fall in blood potassium levels (hypokalemia). Episodes (or attacks) typically involve a temporary weakness or inability to move muscles in the arms and legs. On set of episodes usually occur in childhood or adolescence. These episodes can last for hours or days, and frequency varies among patients. The frequency is usually highest between the ages of 15 and 35, and then decreases with age. Some people with HypoPP also develop late-onset proximal myopathy. Triggers to be avoided include carbohydrates, salt (sodium), cold, repetitive exercise, epinephrine, and steroids.
HypoPP can be caused by mutations in the CACNA1S or SCN4A gene. Inheritance is autosomal dominant. Treatment varies depending on the intensity and duration of attacks. Minor attacks may go away on their own, while treatment for moderate to severe attacks may involve taking oral potassium or intravenous (IV) potassium.
Hyperkalemic periodic paralysis HyperKPP is a genetic disease that causes episodes of extreme muscle weakness associated with an increase of the potassium levels in the blood. Muscle weakness during an attack usually affects the arms and legs and muscles of the eyes, throat, and trunk. Most often, these episodes involve a temporary inability to move muscles in the arms and legs. Episodes usually begin before age 20, most commonly between infancy and age 10. Normally an episode lasts for 15 minutes to an hour, but in some people the episodes may last a few days to a week. Episodes tend to increase in frequency until about age 50, after which they may occur less frequently. Factors that can trigger attacks include rest after strenuous exercise, potassium-rich foods, stress, fatigue, and exposure to cold. Depolarizing anesthetics must be avoided. Muscle strength usually returns to normal between episodes, although many people continue to experience mild stiffness, particularly in muscles of the face and hands. Studies suggest more than 80% of people with hyperkalemic periodic paralysis over age 40 have permanent muscle weakness, most often affecting the leg muscles. About one third may develop a chronic progressive myopathy.
Hyperkalemic periodic paralysis is caused by mutations in the SCN4A gene and is inherited in an autosomal dominant manner. Diagnosis is based on clinical symptoms including the increase of blood potassium level during an episode, but normal levels of blood potassium in between episodes. Genetic testing can confirm the diagnosis. Treatment is focused on avoiding triggers and decreasing the severity of an episode. At the first sign of muscle weakness, episodes in many people may be prevented or stopped by mild exercise and/or eating carbohydrates, inhalation of salbutamol, or intravenous calcium gluconate.
Thyrotoxic periodic paralysis (TPP) is an uncommon but dangerous complication seen in thyrotoxic patients. It is characterized by hypokalemia associated with acute proximal symmetrical lower limb weakness and can progress to involve all four limbs and the respiratory musculature. The mechanisms of hypokalemia are not completely understood. The prevailing theories include increased Na-K ATPase pump activity and mutations in genes encoding inward-rectifier potassium channels in skeletal muscle. It is often confused with familial periodic paralysis (FPP) due to the similarity in presentation but can be differentiated based on the presence of thyrotoxic features and biochemical testing. Commonly recorded and described in East Asian males, the incidence of TPP has been rising in the West and other parts of the world. Knowledge regarding identification, early treatment, and prevention of future episodes of TPP is essential in mitigating this potentially lethal complication.
TPP can be caused by mutations on the KCNJ18 gene. Any cause of hyperthyroidism can lead to thyrotoxic periodic paralysis. They include Graves disease (most common), toxic nodular goiter, solitary toxic nodule, iodine-induced thyrotoxicosis, excess exogenous thyroxine use, thyroiditis, thyrotropin-secreting pituitary adenoma, and amiodarone-induced thyrotoxicosis.
Common factors triggering attacks of periodic paralysis include the consumption of carbohydrate-rich foods, strenuous physical activity, high salt/sodium intake, stresses (surgical, infectious, psychological), trauma, and medications (diuretics, estrogens, acetazolamide, epinephrine, laxatives, corticosteroids, non-steroidal anti-inflammatory drugs, licorice, fluoroquinolones, aminoglycosides, and ecstasy). Andersen-Tawil Syndrome (ATS) also known as long QT syndrome, presents as either hypokalemic or hyperkalemic….