Ion Channel Diseases

Periodic paralyses (hyperkalemic, hypokalemic, Andersen-Tawil syndrome)

What is periodic paralysis?

The different types of periodic paralyses are distinguished by what happens to potassium levels in the blood (specifically the serum, or fluid, portion of the blood).

In the hyperkalemic type (hyperKPP), high serum potassium levels cause attacks of temporary muscle weakness that can result in paralysis when severe. In the hypokalemic type (hypoKPP), low serum potassium levels can trigger attacks. (Kalemic refers to potassium; hyper means too much and hypo too little.) In the Andersen-Tawil type, irregularities in the potassium channel gene can affect the heartbeat as well as the ability of muscles to stay ready to contract.

For more, see Signs and Symptoms.

Hyperkalemic periodic paralysis

What is hyperkalemic periodic paralysis (HyperKPP)?

HyperKPP is one of a group of diseases, called inherited myopathies, that causes problems with the tone and contraction of skeletal muscles. As in all forms of periodic paralysis, episodes of weakness in hyperKPP are caused by a temporary loss of muscle excitability.

What are the symptoms of hyperKPP?

Attacks of weakness usually last 15 minutes to an hour but can last for a day or more. In severe cases, these attacks may recur frequently. They commonly occur after vigorous exercise followed by rest, and can be aggravated by stress, pregnancy or foods high in potassium. During attacks not caused by excess potassium intake, a person can become hyperkalemic or remain normokalemic (with no change in serum potassium levels). Muscle stiffness (myotonia) also can occur.

What causes hyperKPP?

In hyperkalemic periodic paralysis, high levels of potassium in the blood interact with genetically caused abnormalities in sodium channels (pores that allow the passage of sodium molecules) in muscle cells, resulting in temporary muscle weakness and, when severe, in temporary paralysis. The disease is inherited in an autosomal dominant pattern, meaning it is produced by a defective gene contributed by one parent. For more, see Causes/Inheritance.

What is the progression of hyperKPP?

HyperKPP has its onset in childhood. Unlike the case for most myopathies, some people with hyperKPP experience progressive, permanent muscle damage that occurs independently of the attacks. The frequency of attacks declines after middle age. Men and women are affected equally.

What is the status of research on hyperKPP?

MDA continues to support scientists in their quest to understand the molecular bases of inherited myopathies and to find effective treatments.

For more on the periodic paralyses, please see the 2009 report In Focus: Periodic Paralysis.

Hypokalemic periodic paralysis

What is hypokalemic periodic paralysis (hypoKPP)?

HypoKPP is one of a group of diseases, called inherited myopathies, that causes problems with the tone and contraction of skeletal muscles. As in all forms of periodic paralysis, episodes of weakness in hypoKPP are caused by a temporary loss of muscle excitability.

What are the symptoms of hypoKPP?

Attacks of weakness can occur daily and usually happen in the morning (during waking) or at night. Some people with the disease might experience only a few mild attacks in their lifetime. But the most profound attacks can cause nearly full-blown paralysis, and permanent muscle damage may occur.

What causes hypoKPP?

This disease may be caused by genetic defects in either the calcium channel or the sodium channel. The mutations cause a loss of muscle excitability when serum potassium is low. HypoKPP is inherited in anautosomal dominant pattern, meaning it is produced by a defective gene contributed by one parent. For more, see Causes/Inheritance.

What is the progression of hypoKPP?

HypoKPP can have its onset anywhere from early childhood to adulthood. Slowly progressive, permanent weakness in the legs often develops after age 50. Men and women are equally affected.

What is the status of research on hypoKPP?

MDA continues to support scientists in their quest to understand the molecular bases of inherited myopathies and to find effective treatments.

For more on the periodic paralyses, please see the 2009 report In Focus: Periodic Paralysis.

Andersen-Tawil syndrome

What is Andersen-Tawil syndrome?

Andersen-Tawil syndrome is one of a group of diseases, called inherited myopathies, that causes problems with the tone and contraction of skeletal muscles. It is considered more dangerous than the other periodic paralyses because of its potential to induce serious abnormalities in heart rhythm.

Andersen-Tawil syndrome is named for Danish physician Ellen Andersen, who first described the disorder in 1971, and Rabi Tawil, co-director of the MDA clinic in Rochester, N.Y., who refined the diagnostic criteria in the early 2000s.

What are the symptoms of Andersen-Tawil syndrome?

Periodic episodes of weakness lasting hours to days may occur, as can severe heartbeat irregularities, sometimes accompanied by loss of consciousness.

What causes Andersen-Tawil syndrome?

This disease is caused by defects in a potassium channel normally present in skeletal and cardiac muscles. Mutations in this potassium channel gene interfere with the ability of a muscle to stay poised and ready to contract. As a result, periodic episodes of paralysis may occur, and the heartbeat can become irregular. Andersen-Tawil syndrome is inherited in an autosomal dominant pattern, meaning it is produced by a defective gene contributed by one parent. For more, see Causes/Inheritance.

What is the progression of Andersen-Tawil syndrome?

This disease has its onset in childhood or adolescence, and is slowly progressive. Pernament weakness may occur with age. Men and women are affected equally.

What is the status of research in Andersen-Tawil syndrome?

MDA-supported researchers are studying how mutations in genes affect channel function and muscle contraction; creating mouse models of the periodic paralyses; and identifying the characteristics of Andersen-Tawil syndrome. For more, see Research.

For more on the periodic paralyses, please see the 2009 report In Focus: Periodic Paralysis.