Introduction
A familial periodic paralysis is characterized by episodes of flaccid paralysis, loss of deep tendon reflexes, and the inability of muscles to respond to electrical stimulation. It is a rare autosomal dominant condition. The four types are Andersen-Tawil syndrome, thyrotoxic, hypokalemic, and hyperkalemic. Each type of familial periodic paralysis is caused by a unique gene and electrolyte channel.
Approximately, 70 percent of those with the hypokalemic form have a mutation in the voltage-sensitive muscle calcium channel gene's alpha subunit on chromosome 1q (HypoPP type I). The alpha-subunit sodium channel gene on chromosome 17 is mutated in some families (HypoPP type II). Although familial periodic paralysis has several different forms, the hypokalemic form is the most prevalent, with a prevalence of 1 in 100,000.
What Is Hypokalemic Periodic Paralysis?
Hypokalemic periodic paralysis (HypoKPP) is a rare condition marked by the incidence of episodic severe muscle weakness, which is stimulated by strenuous exercise or a high carbohydrate diet. Low serum potassium levels are associated with hypoKPP episodes. The HypoKPP is mostly hereditary or familial. The familial pattern of HypoKPP is a rare channelopathy that primarily affects skeletal muscle cells and is brought on by a mutation in one of the calcium or sodium ion channels. Additionally, acquired cases of HypoKPP are linked to hyperthyroidism. The first descriptions of hypokalemic periodic paralysis were made in 1727 by Musgrave, in 1853 by Cavare, and in 1857 by Romberg.
What Are the Causes of Hypokalemic Periodic Paralysis?
Hypokalemic periodic paralysis has inherited or familial as well as acquired causes. Several mutations have been identified as causes of HypoKPP over the last few decades. Type 1 HypoKPP, the most common familial form, is caused by a mutation in the dihydropyridine-sensitive skeletal muscle calcium channel gene (CACNA1S). Type 2 HypoKPPon the other hand, has mutations in the voltage-sensitive skeletal muscle sodium channel gene (SCN4A). It has also been discovered that the inward rectifier potassium (Kir) channel-coding genes KCNJ2 and KCNJ18 contain disease-causing mutations. Thyrotoxicosis has been linked to acquired HypoKPP. The primary HypoKPP is composed of the familial form and thyrotoxic HypoKPP. Hypokalemia secondary to renal and gastrointestinal potassium loss, such as in renal tubular acidosis, gastroenteritis, or secondary to endocrine causes, can also result in sporadic muscle weakness.
How Is Familial Hypokalemic Periodic Paralysis Diagnosed?
When someone experiences an acute attack of flaccid muscle weakness affecting the proximal muscles with diminished or normal deep tendon reflexes initiated by the triggering factors, then hypokalemic periodic paralysis is suspected. If there is a positive family history or prior personal history of similar attacks of muscle weakness, the suspicion is increased even more. There is no need for additional diagnostic testing to confirm the diagnosis of an episode of paralytic attack when there is a documented family history of hypokalemic periodic paralysis. Otherwise, the diagnosis is made when a typical attack of weakness is accompanied by a low serum potassium level.
The diagnosis of HypoKPP can be difficult both during and after an attack. A secondary cause of hypokalemia, such as distal renal tubular acidosis, is typically characterized by low serum potassium levels between attacks. Other diagnostic options include electromyography, genetic testing, and provocative testing (EMG). In a long exercise test for the diagnosis of HypoKPP between attacks of muscle weakness, the abduction range of the little finger is measured in postexercise and can be a potential substitute parameter to CAMP. Typically, an inter-attack muscle biopsy is not done to confirm the diagnosis. Vacuolar changes or tubular aggregates may be present, but these are non-specific findings for any periodic paralysis.
What Are the Complications of Familial Hypokalemic Periodic Paralysis?
During a muscle weakness attack, immediate life-threatening complications can occur:
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Hypokalemia-related cardiac arrhythmias.
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Respiratory insufficiency is brought on by paralyzed respiratory muscles.
Cardiac arrhythmias are uncommon but have been reported during episodes of muscle weakness in hypokalemic periodic paralysis.
What Is the Prognosis of Familial Hypokalemic Periodic Paralysis?
Individuals with HypoKPP have different prognosis. Oral potassium administration has positive effects on muscle weakness attacks. Repeated episodes of muscle weakness can have a negative impact on a patient's social and professional life by increasing hospital admissions, causing significant morbidity, and causing frequent attacks of weakness. Although aspiration pneumonia has been linked to a number of deaths, deaths from muscle attacks are relatively uncommon.
What Is the Treatment of Familial Hypokalemic Periodic Paralysis?
The main objectives of treatment are to reduce acute attack symptoms, manage any immediate complications that may arise, and prevent late complications and additional attacks.
Acute Treatment:
It is intended to stabilize the serum potassium level by giving oral potassium chloride, which is thought to be more easily absorbed than other oral potassium solutions and relieves the symptoms of muscle weakness. Oral potassium chloride is given in incremental doses, with a reasonable starting dose of 0.5 to 1 mEq/kg (or 60 to 120 mEq of potassium for a 60 kg person). If the first dose is ineffective, 30 % of the first dose or 0.3 mEq/kg and is repeated every 30 minutes. Close monitoring of serum potassium levels is necessary if the patient needs to take more than 100 mEq of oral potassium, and the total dose of oral potassium should not exceed 200 mEq in any 24-hour period. Depending on the degree of hypokalemia, the initial dose of oral potassium may change. Muscle strength should be regularly assessed, and patients should be kept under ECG (electrocardiography) monitoring. The posttreatment rise in serum potassium level should be monitored for 24 hours because it may negatively affect patients. Low-intensity exercises can also be beneficial for people who experience milder forms of attacks.
Preventive Treatment:
Interventions that use both pharmaceutical and nonpharmacological approaches can be used to stop recurrent attacks in the future. Nonpharmacological approaches involve educating patients about potential triggers and making lifestyle changes to avoid them. When lifestyle changes are no longer sufficient to lower attack rates, pharmacologic interventions such as carbonic anhydrase inhibitors (CAIs), potassium-sparing diuretics, and chronic potassium supplementation are used. The preferred method is to combine a diuretic with chronic potassium supplementation. Acetazolamide, a carbonic anhydrase inhibitor, is typically used as a diuretic.
Conclusion:
One of the most important aspects of treating hypokalemic periodic paralysis is patient education. In addition to preventing future attacks, reducing recurrent hospital admissions, decreasing patient morbidity, and improving quality of life, educating patients about their disease process and advising them to avoid the trigger factors through lifestyle and behavioral changes can also help to lessen the financial burden associated with hospital readmissions. It is important to identify the triggering factors in each person because they can differ. Avoiding strenuous exercise, eating small, frequent meals to avoid carbohydrate load, consuming less salt, avoiding stressful situations, and remaining active to avoid prolonged immobilization can all help prevent attacks.
