familial periodic paralysis

Familial periodic paralysis is a group of rare genetic neurological disorders caused by mutations in genes that regulate sodium and calcium channels in nerve cells [1, 10, 11]. These disorders are characterized by episodes of muscle weakness or paralysis, which can be triggered by various factors such as changes in potassium levels, exercise, or emotional stress [2, 5, 7].

There are four main forms of familial periodic paralysis: hypokalemic, hyperkalemic, thyrotoxic, and Andersen-Tawil syndrome [11]. Hypokalemic periodic paralysis is the most common type, characterized by a fall in potassium levels, which can lead to muscle weakness or paralysis [3, 13].

The symptoms of familial periodic paralysis can vary depending on the specific form of the disorder. However, they often include episodes of flaccid paralysis with loss of deep tendon reflexes and failure of muscle to respond to electrical stimulation [4, 11]. Between episodes, the affected muscles usually work normally.

Familial periodic paralyses are inherited in an autosomal dominant pattern, meaning that only one parent needs to carry the gene mutation for their children to be affected [14]. However, not all family members who share the gene are affected to the same degree, and there can be considerable variation in penetrance [11].

Overall, familial periodic paralysis is a rare and complex condition that requires careful diagnosis and management by a healthcare professional.

Familial periodic paralysis is a rare autosomal dominant condition characterized by episodes of flaccid paralysis with loss of deep tendon reflexes and failure of muscle to respond to electrical stimulation [12]. The symptoms of this condition can vary depending on the type, but common signs and symptoms include:

• Episodes of muscle weakness or loss of muscle movement (paralysis) that come and go [8][9]
• Normal muscle strength between attacks [8][9]
• Attacks often triggered by strenuous exercise, high carbohydrate meals, injection of insulin, glucose, or epinephrine [2][3]
• Weakness may be mild and limited to certain muscle groups, or more severe and affect the arms and legs [2]
• Episodes usually begin before age 16 in hypokalemic periodic paralysis [10]

In addition to these general symptoms, there are four forms of familial periodic paralysis, each with its own unique characteristics:

• Hypokalemic Periodic Paralysis: characterized by a fall in potassium levels in the blood, attacks often triggered by strenuous exercise or high carbohydrate meals [2][3]
• Hyperkalemic Periodic Paralysis: signs and symptoms usually begin in children younger than 10 years old, with stiffness or heaviness to the muscles that begins in the thighs and spreads to other parts of the body [15]
• Thyrotoxic Periodic Paralysis: caused by low levels of potassium in the blood, people also have signs of an overactive thyroid gland (hyperthyroidism) [1]
• Andersen-Tawil Syndrome: potassium levels can be high, low, or normal, symptoms include episodes of muscle weakness or paralysis that come and go [12]

It's worth noting that these symptoms can vary in severity and frequency from person to person, and may not always be present. If you suspect you or a family member has familial periodic paralysis, it's essential to consult with a medical professional for proper diagnosis and treatment.

Diagnostic Tests for Familial Periodic Paralysis

Familial periodic paralysis, also known as familial hypokalemic or hyperkalemic periodic paralysis, is a rare inherited disorder that causes sudden attacks of weakness and paralysis. Diagnosing this condition can be challenging, but several diagnostic tests can help confirm the diagnosis.

Blood Potassium Level Test

Measuring the blood potassium level during an attack is one of the best tests to diagnose familial hypokalemic periodic paralysis (FHPP). A significant drop in potassium levels (<3.5 mmol/L) during attacks can indicate FHPP [12]. This test is often used in conjunction with other diagnostic tests.

Exercise Test

A potassium exercise test, also known as a long exercise test, can be useful in diagnosing familial hypokalemic periodic paralysis (FHOPP). This test involves measuring the blood potassium level before and after exercise. A ≥ 40% decrease postexercise is abnormal and consistent with FHPP [1].

Genetic Testing

Genetic testing can also help diagnose familial periodic paralysis. A periodic paralysis gene panel test can identify genetic mutations associated with this condition [5]. This test is particularly useful for patients with a clinical suspicion of periodic paralysis.

Other Diagnostic Tests

Other diagnostic tests that may be used to rule out other conditions or confirm the diagnosis include:

• Electrolyte profile, ECG, and strength testing every 15 minutes for 2 hours and then every 30 minutes for the next 2 hours [4]
• Dynamometry and muscle CT-scanning [6]
• Genetic tests for other conditions such as Bartter’s syndrome, Gitelman’s syndrome, RTA 1, RTA 2, Liddle’s syndrome, myasthenia gravis, and narcolepsy [10]

Conclusion

Diagnosing familial periodic paralysis requires a comprehensive approach that includes measuring blood potassium levels during attacks, exercise testing, genetic testing, and other diagnostic tests. A correct diagnosis is essential for effective management of this condition.

References:

[1] Context 2 [4] Context 4 [5] Context 5 [6] Context 6 [10] Context 10 [12] Context 12

Treatment Options for Familial Periodic Paralysis

Familial periodic paralysis, a rare autosomal dominant condition, can be effectively managed with various treatment options. The primary goal is to prevent or alleviate episodes of muscle weakness or paralysis.

• Dichlorphenamide: This medication has been approved by the FDA for the treatment of familial hypokalemic periodic paralysis (FHP). It works by inhibiting carbonic anhydrase, which helps regulate potassium levels in the blood. [1][2]
• Acetazolamide: Another carbonic anhydrase inhibitor, acetazolamide is sometimes used to treat FHP, although its effectiveness may vary depending on individual cases. [3][4]
• KEVEYIS: This FDA-approved treatment is specifically designed for primary hyperkalemic periodic paralysis (PHPP), but it can also be effective in treating other similar conditions, including FHP. KEVEYIS works by inhibiting the sodium-potassium pump, which helps regulate potassium levels in the blood. [5][6]
• Potassium supplements: In some cases, potassium supplements may be prescribed to help manage episodes of muscle weakness or paralysis. However, this should only be done under medical supervision, as excessive potassium intake can lead to other complications. [7]

Other Treatment Considerations

In addition to these medications, other treatment options may include:

• Dietary modifications: Making changes to one's diet, such as avoiding high-carbohydrate meals or strenuous exercise, can help prevent episodes of muscle weakness or paralysis.
• Potassium-retaining drugs: In some cases, potassium-retaining drugs like potassium citrate or potassium gluconate may be prescribed to help manage potassium levels in the blood. [8]

Important Notes

It's essential to note that each individual case of familial periodic paralysis is unique, and treatment plans should be tailored to meet specific needs. Consultation with a healthcare professional is crucial for determining the most effective course of treatment.

References:

[1] Dalakas MC. (1983) Dichlorophenamide in the treatment of patients with HOPP-associated interattack muscle

Familial Periodic Paralysis Differential Diagnoses

Familial periodic paralysis (FPP) is a rare neuromuscular disorder characterized by recurring episodes of muscle weakness or paralysis. When considering the differential diagnosis for FPP, several conditions should be taken into account.

• Hyperkalemic and Hypokalemic Periodic Paralyses: These are the most common forms of periodic paralysis, caused by mutations in skeletal muscle sodium, calcium, and potassium channel genes [2]. The diagnosis is based on clinical presentation, including episodes of muscle weakness or paralysis, and documented serum potassium levels.
• Andersen-Tawil Syndrome: This rare genetic disorder can also cause periodic paralysis, characterized by episodes of muscle weakness or paralysis, often associated with cardiac abnormalities [4].
• Secondary Hypokalemic Periodic Paralysis: This condition is caused by underlying renal or endocrine diseases that lead to hypokalemia (low potassium levels) and subsequent muscle weakness or paralysis [4].

Other Differential Diagnoses

In addition to the above conditions, other neuromuscular disorders should be considered in the differential diagnosis of FPP:

• Guillain-Barré Syndrome: An autoimmune disorder that can cause muscle weakness or paralysis, often accompanied by sensory symptoms [5].
• Polymyositis: A rare inflammatory muscle disease that can lead to muscle weakness or paralysis [5].
• Myasthenia Gravis: A chronic autoimmune disorder that affects the nerve-muscle connection, leading to muscle weakness or paralysis [5].

Genetic Considerations

It's essential to note that up to 30% of patients with FPP may not have a detectable genetic mutation [6]. Therefore, other factors such as environmental triggers or undiagnosed secondary conditions should be considered in the differential diagnosis.

References:

[2] Periodic paralyses (PPs) are rare neuromuscular disorders caused by mutations in skeletal muscle sodium, calcium, and potassium channel genes. [4] Differential diagnoses should include hyper/normokalemic periodic paralysis, Andersen-Tawil syndrome and secondary hypoPP caused by renal or endocrine diseases... [5] In addition to TPP, the differential diagnosis of lower limb paralysis includes: Guillain-Barre syndrome, polymyositis, myasthenia gravis, acute intermittent... [6] You may have an as of yet undescribed mutation. • Up to 30% of patients are mutation negative! Page 17. Genes causing Periodic Paralysis.