Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Hyperkalemic periodic paralysis

Laurie Gutmann, MD
Robin Conwit, MD
Section Editor
Jeremy M Shefner, MD, PhD
Deputy Editor
Janet L Wilterdink, MD


Periodic paralysis is a muscle disease that causes episodic muscle weakness, in the family of diseases called channelopathies. It is classified as hypokalemic when episodes occur in association with low potassium blood levels or as hyperkalemic when episodes can be induced by elevated potassium. Most cases of periodic paralysis are hereditary, usually with an autosomal dominant inheritance pattern [1,2].

Hyperkalemic periodic paralysis is a muscle disease that has onset in infancy or early childhood and is manifested by transient episodes of paralysis, usually precipitated by cold exposure, rest after exercise, fasting, or the ingestion of small amounts of potassium [1,2]. The first description in 1951 was of a family with frequent attacks of paralysis that were of short duration and precipitated by rest after exercise, stress, and certain foods [3]. Later, an important observation made was that potassium levels were high in some patients and potassium administration frequently precipitated these attacks [4].

This topic discusses hyperkalemic periodic paralysis. Other causes of periodic paralysis are discussed separately. (See "Hypokalemic periodic paralysis" and "Thyrotoxic periodic paralysis".)


Hyperkalemic periodic paralysis (PP) is a rare disorder, with an estimated prevalence of 1:200,000 [5]. Women and men appear to be equally affected.


Hyperkalemic PP is an autosomal dominant condition with nearly complete penetrance. The cause of hyperkalemic PP is a change in a gene that regulates the production of a protein (SCN4A) in the sodium channel of skeletal muscle. The gene is located in chromosome 17q23, and is known as SCN4A [1,2,6,7]. At least nine different mutations in this gene have been identified that can cause hyperkalemic PP [5,7,8].

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Jun 13, 2014.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Fontaine B, Lapie P, Plassart E, et al. Periodic paralysis and voltage-gated ion channels. Kidney Int 1996; 49:9.
  2. Miller TM, Dias da Silva MR, Miller HA, et al. Correlating phenotype and genotype in the periodic paralyses. Neurology 2004; 63:1647.
  3. TYLER FH, STEPHENS FE, GUNN FD, PERKOFF GT. Studies in disorders of muscle. VII. Clinical manifestations and inheritance of a type of periodic paralysis without hypopotassemia. J Clin Invest 1951; 30:492.
  4. GAMSTORP I. [Not Available]. Acta Paediatr Suppl 1956; 45:1.
  5. Jurkat-Rott K, Lehmann-Horn F. Genotype-phenotype correlation and therapeutic rationale in hyperkalemic periodic paralysis. Neurotherapeutics 2007; 4:216.
  6. Rojas CV, Wang JZ, Schwartz LS, et al. A Met-to-Val mutation in the skeletal muscle Na+ channel alpha-subunit in hyperkalaemic periodic paralysis. Nature 1991; 354:387.
  7. Fontaine B, Khurana TS, Hoffman EP, et al. Hyperkalemic periodic paralysis and the adult muscle sodium channel alpha-subunit gene. Science 1990; 250:1000.
  8. Lossin C, Nam TS, Shahangian S, et al. Altered fast and slow inactivation of the N440K Nav1.4 mutant in a periodic paralysis syndrome. Neurology 2012; 79:1033.
  9. Lehmann-Horn F, Küther G, Ricker K, et al. Adynamia episodica hereditaria with myotonia: a non-inactivating sodium current and the effect of extracellular pH. Muscle Nerve 1987; 10:363.
  10. Weber MA, Nielles-Vallespin S, Essig M, et al. Muscle Na+ channelopathies: MRI detects intracellular 23Na accumulation during episodic weakness. Neurology 2006; 67:1151.
  11. Bendahhou S, Cummins TR, Kula RW, et al. Impairment of slow inactivation as a common mechanism for periodic paralysis in DIIS4-S5. Neurology 2002; 58:1266.
  12. Vicart S, Sternberg D, Fournier E, et al. New mutations of SCN4A cause a potassium-sensitive normokalemic periodic paralysis. Neurology 2004; 63:2120.
  13. Gould RJ, Steeg CN, Eastwood AB, et al. Potentially fatal cardiac dysrhythmia and hyperkalemic periodic paralysis. Neurology 1985; 35:1208.
  14. Lisak RP, Lebeau J, Tucker SH, Rowland LP. Hyperkalemic periodic paralysis and cardiac arrhythmia. Neurology 1972; 22:810.
  15. Yoshimura T, Kaneuji M, Okuno T, et al. Periodic paralysis with cardiac arrhythmia. Eur J Pediatr 1983; 140:338.
  16. Cannon SC, George AL. Pathophysiology of myotonia and periodic paralysis. In: Diseases of the Nervous System, 3rd, Asbury AK, McKhann GM, McDonald WI, et al (Eds), Cambridge University Press, Cambridge 2002. p.1183.
  17. Bradley WG, Taylor R, Rice DR, et al. Progressive myopathy in hyperkalemic periodic paralysis. Arch Neurol 1990; 47:1013.
  18. Venance SL, Cannon SC, Fialho D, et al. The primary periodic paralyses: diagnosis, pathogenesis and treatment. Brain 2006; 129:8.
  19. Fontaine B. Periodic paralysis. Adv Genet 2008; 63:3.
  20. McManis PG, Lambert EH, Daube JR. The exercise test in periodic paralysis. Muscle Nerve 1986; 9:704.
  21. Kuntzer T, Flocard F, Vial C, et al. Exercise test in muscle channelopathies and other muscle disorders. Muscle Nerve 2000; 23:1089.
  22. Fournier E, Arzel M, Sternberg D, et al. Electromyography guides toward subgroups of mutations in muscle channelopathies. Ann Neurol 2004; 56:650.
  23. Streeten DH, Speller PJ, Fellerman H. Use of corticotropin-induced potassium changes in the diagnosis of both hypo- and hyperkalemic periodic paralysis. Eur Neurol 1993; 33:103.
  24. Hanna MG, Stewart J, Schapira AH, et al. Salbutamol treatment in a patient with hyperkalaemic periodic paralysis due to a mutation in the skeletal muscle sodium channel gene (SCN4A). J Neurol Neurosurg Psychiatry 1998; 65:248.
  25. Götze FR, Thid S, Kyllerman M. Fibromyalgia in hyperkalemic periodic paralysis. Scand J Rheumatol 1998; 27:383.
  26. Bendheim PE, Reale EO, Berg BO. beta-Adrenergic treatment of hyperkalemic periodic paralysis. Neurology 1985; 35:746.
  27. Wang P, Clausen T. Treatment of attacks in hyperkalaemic familial periodic paralysis by inhalation of salbutamol. Lancet 1976; 1:221.
  28. Ricker K, Camacho LM, Grafe P, et al. Adynamia episodica hereditaria: what causes the weakness? Muscle Nerve 1989; 12:883.
  29. Chinnery PF, Walls TJ, Hanna MG, et al. Normokalemic periodic paralysis revisited: does it exist? Ann Neurol 2002; 52:251.
  30. Tawil R, McDermott MP, Brown R Jr, et al. Randomized trials of dichlorphenamide in the periodic paralyses. Working Group on Periodic Paralysis. Ann Neurol 2000; 47:46.
  31. Sansone V, Meola G, Links TP, et al. Treatment for periodic paralysis. Cochrane Database Syst Rev 2008; :CD005045.
  32. Riggs JE, Griggs RC, Moxley RT 3rd, Lewis ED. Acute effects of acetazolamide in hyperkalemic periodic paralysis. Neurology 1981; 31:725.
  33. Klingler W, Lehmann-Horn F, Jurkat-Rott K. Complications of anaesthesia in neuromuscular disorders. Neuromuscul Disord 2005; 15:195.
  34. Thiel A, Wagner M, Behr R, Hempelmann G. [Anesthesia in familial hyperkalemic periodic paralysis]. Anasthesiol Intensivmed Notfallmed Schmerzther 1993; 28:125.
  35. Russell SH, Hirsch NP. Anaesthesia and myotonia. Br J Anaesth 1994; 72:210.
  36. Neuman GG, Kopman AF. Dyskalemic periodic paralysis and myotonia. Anesth Analg 1993; 76:426.