What are the other Names for this Condition? (Also known as/Synonyms)

• Adynamia Episodica Hereditaria with or without Myotonia
• Gamstorp Disease
• HyperPP (Hyperkalemic Periodic Paralysis)

What is Hyperkalemic Periodic Paralysis? (Definition/Background Information)

• Hyperkalemic Periodic Paralysis (HyperPP) is a genetic disease that causes episodes of extreme muscle weakness and 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, usually 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 should also 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 level 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

(Source: Hyperkalemic Periodic Paralysis; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Hyperkalemic Periodic Paralysis? (Age and Sex Distribution)

• Hyperkalemic Periodic Paralysis is a rare congenital disorder. However, the presentation of symptoms may occur any time after birth
• The peak period of onset is between birth and up to age 10. In many cases, the onset occurs before the individual reaches young adulthood (age 20 years or less)
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Hyperkalemic Periodic Paralysis? (Predisposing Factors)

• A positive family history may be an important risk factor, since Hyperkalemic Periodic Paralysis is an inherited condition
• Currently, no other risk factors have been clearly identified for the disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Hyperkalemic Periodic Paralysis? (Etiology)

• Hyperkalemic Periodic Paralysis is caused by mutations in the SCN4A gene and is inherited in an autosomal dominant manner

(Source: Hyperkalemic Periodic Paralysis; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Autosomal dominant: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of Hyperkalemic Periodic Paralysis?

The signs and symptoms of Hyperkalemic Periodic Paralysis may include:

Very frequently present symptoms in 80-99% of the cases:

• Cerebral palsy
• Elevated serum creatine phosphokinase
• EMG abnormality
• Episodic flaccid weakness
• Periodic hyperkalemic paralysis

Frequently present symptoms in 30-79% of the cases:

• Fasciculations
• Gait disturbance
• Hyperkalemia
• Myalgia
• Myotonia

Occasionally present symptoms in 5-29% of the cases:

• Arrhythmia
• Bowel incontinence
• Chest pain
• Congestive heart failure
• Feeding difficulties in infancy
• Flexion contracture
• Hypertonia
• Hypokalemia
• Hyponatremia
• Malignant hyperthermia
• Myopathy
• Ophthalmoparesis
• Paresthesia
• Respiratory insufficiency
• Skeletal muscle atrophy
• Skeletal muscle hypertrophy

(Source: Hyperkalemic Periodic Paralysis; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Hyperkalemic Periodic Paralysis Diagnosed?

Hyperkalemic Periodic Paralysis is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Hyperkalemic Periodic Paralysis?

The complications of Hyperkalemic Periodic Paralysis may include:

• Severe neurological abnormalities
• Breathing difficulties
• Immobility and paralysis
• Death in infancy or even during early adulthood is a possibility in some cases

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Hyperkalemic Periodic Paralysis Treated?

• The treatment of Hyperkalemic Periodic Paralysis 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

The medication(s) listed below have been approved by the US Food and Drug Administration (FDA) as ‘orphan products’ for treatment of this condition.

FDA-approved indication - ﷟HYPERLINK "https://rarediseases.info.nih.gov/diseases/fda-orphan-drugs"Dichlorphenamide: Treatment of primary Hyperkalemic Periodic Paralysis, Primary Hypokalemic Periodic Paralysis, and related variants.

(Source: Hyperkalemic Periodic Paralysis; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How can Hyperkalemic Periodic Paralysis be Prevented?

Currently, Hyperkalemic Periodic Paralysis may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Hyperkalemic Periodic Paralysis? (Outcomes/Resolutions)

• The prognosis of Hyperkalemic Periodic Paralysis is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Hyperkalemic Periodic Paralysis:

Hyperkalemic Periodic Paralysis is also known by the following names:

• Gamstorp Episodic Adynamy
• HyperKPP (Hyperkalemic Periodic Paralysis)
• HYPP (Hyperkalemic Periodic Paralysis)
• Sodium Channel Muscle Disease

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/