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Hypokalemic Periodic Paralysis.

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GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014.
2002 Apr 30 [updated 2014 Jul 31].

Excerpt

DISEASE CHARACTERISTICS:

Hypokalemic periodic paralysis (HOKPP) is a condition in which affected individuals may experience paralytic episodes with concomitant hypokalemia (<2.5 mmol/L), and occasionally may develop late-onset proximal myopathy. The paralytic attacks are characterized by reversible flaccid paralysis usually leading to paraparesis or tetraparesis but typically sparing the respiratory muscles and heart. Acute paralytic crises usually last at least several hours and sometimes days. Some individuals have only one episode in a lifetime; more commonly, crises occur repeatedly: daily, weekly, monthly, or less often. The major triggering factors are carbohydrate-rich meals and rest after exercise; rarely, cold-induced hypokalemic paralysis has been reported. The interval between crises may vary and may be prolonged by preventive treatment with potassium salts or acetazolamide. The age of onset of the first attack ranges from one to 20 years; the frequency of attacks is highest between ages 15 and 35 and then decreases with age. A variable myopathy develops in at least 25% of affected individuals and may result in a progressive fixed muscle weakness that manifests at variable ages as exercise intolerance predominantly in the lower limbs. It may occur independent of paralytic symptoms and may be the sole manifestation of HOKPP. Individuals with HOKPP are at increased risk for pre- or post-anesthetic weakness and may be at an increased risk for malignant hyperthermia – though not as great a risk as in individuals with true autosomal dominant malignant hyperthermia susceptibility (MHS).

DIAGNOSIS/TESTING:

The diagnosis of HOKPP is based on a history of episodes of flaccid paralysis with rapid installation and spontaneous recovery; low serum concentration of potassium (0.9 to 3.0 mmol/L) during attacks, but not between attacks; the identification of typical precipitating factors (i.e., rest after a strong physical exertion, prolonged immobility); and a family history consistent with autosomal dominant inheritance. Of all individuals meeting diagnostic criteria for HOKPP, approximately 60% have mutations in CACNA1S, approximately 20% in SCN4A, and approximately 3.5% in KCNJ18.

MANAGEMENT:

Treatment of manifestations. Treatment varies depending on the intensity and duration of the paralytic attack. Minor attacks may resolve spontaneously. Moderate attacks may be self-treated in a non-medical setting by ingestion of oral potassium salts. Severe attacks typically require more intensive medical management with intravenous potassium infusion, serial measurement of serum potassium concentration, clinical evaluation of possible respiratory involvement, and continuous electrocardiogram monitoring. There is no known curative treatment for HOKPP-related myopathy; physiotherapy may help to maintain strength and motor skills. Prevention of primary manifestations. The goal of preventive treatment is to reduce the frequency and intensity of paralytic attacks. This may be achieved by avoidance of triggering factors; adherance to a diet low in sodium and carbohydrate and rich in potassium; and oral potassium supplementation. If dietary intervention and oral potassium supplementation are not effective in preventing attacks, acetazolamide treatment may be necessary. However, acetazolamide may exacerbate attacks, in which case alternative treatments (e.g., dichlorphenamide, triamterene, spironolactone) may be used. Prevention of secondary complications. Creating a safe environment includes informing companions of the risk of paralytic attacks, educating the affected individual to ask for medical help in case of an unusually severe attack, and home modification to prevent falls and accidents. Anesthetic complications, including malignant hyperthermia, should be prevented by strict control of serum potassium concentration; avoidance of large glucose loads; maintenance of body temperature and acid-base balance; and careful use of neuromuscular blocking agents with continuous monitoring of neuromuscular function. It is unknown whether prevention of paralytic attacks also prevents the development of myopathy. Surveillance. The frequency of consultations is adapted to the individual's signs/symptoms and response to preventive treatment. Periodic neurologic examination with attention to muscle strength in the legs should be performed to detect permanent weakness associated with myopathy. For those taking acetazolamide, the following are indicated every three months: complete blood count, electrolytes, glucose, uric acid, and liver enzyme levels. Renal ultrasound should be performed annually. Agents/circumstances to avoid. Factors that trigger paralytic attacks (e.g., unusually strenuous effort, carbohydrate-rich meals, sweets, alcohol, prolonged immobility, oral or intravenous corticosteroids, glucose infusions) should be avoided when possible. Evaluation of relatives at risk. When the family-specific mutation is known, molecular genetic testing of at-risk, asymptomatic family members can identify those at risk for unexpected acute paralysis and/or anesthetic complications.

GENETIC COUNSELING:

HOKPP is inherited in an autosomal dominant manner. Most individuals diagnosed with HOKPP have an affected parent. The proportion of cases caused by de novo mutation is unknown. Offspring of a proband are at a 50% risk of inheriting the mutation. Penetrance is about 90% in males and may be as low as 50% in females depending on the causative mutation. If the disease-causing allele has been identified in an affected family member, prenatal testing for pregnancies at increased risk may be available from a clinical laboratory that offers either testing for the relevant gene or custom prenatal testing; however, requests for prenatal testing for conditions which (like HOKPP) do not affect intellect, are compatible with a nearly normal life, and have available treatment options are not common.

Copyright © 1993-2014, University of Washington, Seattle. All rights reserved.

PMID:
20301512
[PubMed]
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