Hypokalemic Periodic Paralysis

It is an autosomal dominant muscle disorder in which affected individuals suffer episodes of paralysis and muscle weakness with hypocalcemia that are usually triggered after intense exercise.

Hypokalemic periodic paralysis (hypoPPP) is a rare muscle channelopathy that causes episodes of muscle weakness and paralysis associated with decreased blood potassium levels. It is inherited in an autosomal dominant manner. The genes involved in the development of the disease are CACNA1S and SCN4A encoding muscle ion channel subunits.

The prevalence of the disease is estimated to be between 1-9 cases per 100,000. The onset of hypokalemic periodic paralysis may be in childhood or adolescence, around the second decade of life.

Symptoms

The disease produces attacks of weakness or paralysis that vary from patient to patient. Some people have attacks every day, while others have them once a year. The attacks of weakness or paralysis are characterised by:

Mainly affecting shoulders and hips, and to a lesser extent, arms, legs, eye muscles and muscles involved in breathing and swallowing.
Occur when the person is awake.
Occur intermittently.
Occur most often on waking or after sleep or rest.
Rare during exercise, but may be triggered at rest after exercise.
May be triggered by heavy meals, high carbohydrate, high salt or alcohol consumption.
Typically last from 3 to 24 hours.

Disease management

There is no known cure for hypokalemic periodic paralysis. There are some measures that may help prevent attacks. Taking acetazolamide or dichlorphenamide (carbonic anhydrase inhibitors) or daily potassium supplementation may help prevention. At the dietary level, a low-carbohydrate, potassium-rich diet is recommended. Physical therapy may also help to decrease motor damage.

At the onset of an attack, mild physical activity or oral potassium salts may stop the attack. In the case of a severe attack, medical treatment with intravenous potassium administration is required.

Genes analyzed

CACNA1S SCN4A

Bibliography

Boerman, R. H., Ophoff, R. A., Links, T. P., et al . Mutation in DHP receptor alpha 1 subunit (CACLN1A3) gene in a Dutch family with hypokalaemic periodic paralysis. Journal of medical genetics. 1995 Jan;32(1):44-7.

Bulman, D. E., Scoggan, K. A., van Oene, M. D., et al . A novel sodium channel mutation in a family with hypokalemic periodic paralysis. Neurology. 1999 Dec 10;53(9):1932-6.

Chabrier, S., Monnier, N., Lunardi, J . Early onset of hypokalemic periodic paralysis caused by a novel mutation of the CACNA1S gene. Journal of medical genetics. 2008 Oct;45(10):686-8.

Elbaz, A., Vale-Santos, J., Jurkat-Rott, K., et al . Hypokalemic periodic paralysis and the dihydropyridine receptor (CACNL1A3): genotype/phenotype correlations for two predominant mutations and evidence for the absence of a founder effect in 16 Caucasian families. American journal of human genetics. 1995 Feb;56(2):374-80.

Jurkat-Rott, K., Mitrovic, N., Hang, C., et al . Voltage-sensor sodium channel mutations cause hypokalemic periodic paralysis type 2 by enhanced inactivation and reduced current. Proceedings of the National Academy of Sciences of the United States of America. 2000 Aug 15;97(17):9549-54.

Jurkat-Rott, K., Lehmann-Horn, F., Elbaz, A., et al . A calcium channel mutation causing hypokalemic periodic paralysis. Human molecular genetics. 1994 Aug;3(8):1415-9.

Weber, F., Lehmann-Horn, F. Hypokalemic Periodic Paralysis. In M. P. Adam (Eds.) et al., GeneReviews®. University of Washington, Seattle.