Hyperkalemic periodic paralysis

Definition

Periodic paralysis (PP) is the name for several rare, inherited muscle disorders marked by temporary weakness, especially following rest, sleep, or exercise.

Description

Periodic paralysis disorders are genetic disorders that affect muscle strength. There are two major forms, hypokalemic and hyperkalemic, each caused by defects in different genes.

In hypokalemic PP, the level of potassium in the blood falls in the early stages of a paralytic attack, while in hyperkalemic PP, it rises slightly or is normal. (The root of both words, "kali," refers to potassium.) Hyperkalemic PP is also called potassium-sensitive PP.

Causes & symptoms

Causes

Both forms of PP are caused by inheritance of defective genes. Both genes are dominant, meaning that only one copy of the defective gene is needed for a person to develop the disease. A parent with the gene has a 50% chance of passing it along to each offspring, and the likelihood of passing it on is unaffected by the results of previous pregnancies.

The gene for hypokalemic PP is present equally in both sexes, but leads to noticeable symptoms more often in men than in women. The normal gene is responsible for a muscle protein controlling the flow of calcium during muscle contraction.

The gene for hyperkalemic PP affects virtually all who inherit it, with no difference in male-vs.-female expression. The normal gene is responsible for a muscle protein controlling the flow of sodium during muscle contraction.

Symptoms

The attacks of weakness in hypokalemic PP usually begin in late childhood or early adolescence and often become less frequent during middle age. The majority of patients develop symptoms before age 16. Since they begin in the school years, the symptoms of hypokalemic PP are often first seen during physical education classes or after-school sports, and may be mistaken for laziness, or lack of interest on the part of the child.

Attacks are most commonly brought on by:

• Strenuous exercise followed by a short period of rest
• Large meals, especially ones rich in carbohydrates or salt
• Emotional stress
• Alcohol use
• Infection
• Pregnancy.

The weakness from a particular attack may last from several hours to as long as several days, and may be localized to a particular limb, or might involve the entire body.

The attacks of weakness of hyperkalemic PP usually begin in infancy or early childhood, and may also become less severe later in life. As in the hypokalemic form, attacks are brought on by stress, pregnancy, and exercise followed by rest. In contrast, though, hyperkalemic attacks are not associated with a heavy meal but rather with missing a meal, with high potassium intake, or use of glucocorticoid drugs such as prednisone. (Glucocorticoids are a group of steroids that regulate metabolism and affect muscle tone.)

Weakness usually lasts less than three hours, and often persists for only several minutes. The attacks are usually less severe, but more frequent, than those of the hypokalemic form. Weakness usually progresses from the lower limbs to the upper, and may involve the facial muscles as well.

Diagnosis

Diagnosis of either form of PP begins with a careful medical history and a complete physical and neurological exam. A family medical history may reveal other affected relatives. Blood and urine tests done at the onset of an attack show whether there are elevated or depressed levels of potassium. Electrical tests of muscle and a muscle biopsy show characteristic changes.

Challenge tests, to aid in diagnosis, differ for the two forms. In hypokalemic PP, an attack of weakness can be brought on by administration of glucose and insulin, with exercise if necessary. An attack of hyperkalemic PP can be induced with administration of potassium after exercise during fasting. These tests are potentially hazardous and require careful monitoring.

Genetic tests are available at some research centers and are usually recommended for patients with a known family history. However, the number of different possible mutations leading to each form is too great to allow a single comprehensive test for either form, thus limiting the usefulness of genetic testing.

Treatment

Severe respiratory weakness from hypokalemic PP may require intensive care to ensure adequate ventilation. Potassium chloride may be given by mouth or intravenously to normalize blood levels.

Attacks requiring treatment are much less common in hyperkalemic PP. Glucose and insulin may be prescribed. Eating carbohydrates may also relieve attacks.

Prognosis

Most patients learn to prevent their attacks well enough that no significant deterioration in the quality of life occurs. Strenuous exercise must be avoided, however. Attacks often lessen in severity and frequency during middle age. Frequent or severe attacks increase the likelihood of permanent residual weakness, a risk in both forms of periodic paralysis.

Prevention

There is no way to prevent the occurrence of either disease in a person with the gene for the disease. The likelihood of an attack of either form of PP may be lessened by avoiding the triggers (the events or combinations of circumstances which cause an attack) for each.

Hypokalemic PP attacks may be prevented with use of acetazolamide (or another carbonic anhydrase inhibitor drug) or a diuretic to help retain potassium in the bloodstream. These attacks may also be prevented by avoiding such triggers as salty food, large meals, a high-carbohydrate diet, and strenuous exercise.

Attacks of hyperkalemic PP may be prevented with frequent small meals high in carbohydrates, and the avoidance of foods high in potassium such as orange juice or bananas. Acetazolamide or thiazide (a diuretic) may be prescribed.

Key Terms

Gene

A biologic unit of heredity transmitted from parents to offspring.

Further Reading

For Your Information

Books

• Fauci, Anthony S., et al., eds. Harrison's Principles of Internal Medicine. 14th ed. New York: McGraw-Hill, 1998.
• "The Periodic Paralyses." In Clinical Neurology, edited by Michael Swash and John Oxbury. London: Churchill Livingstone, 1991.

  Organizations

• Muscular Dystrophy Association. 3300 E. Sunrise Dr., Tucson, AZ 85718. http://www.mdausa.org.
• The Periodic Paralysis Association. 5225 Canyon Crest Drive #71-351, Riverside, CA 92507. (909) 781-4401. http://www.periodicparalysis.org.

Gale Encyclopedia of Medicine. Gale Research, 1999.