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hypokalemic periodic paralysis

MIM.170400

Tuesday 5 August 2008

Hypokalemic periodic paralysis is the most common periodic paralysis, with a prevalence of approximately 1:100,000. Inheritance is autosomal-dominant, with a reduced penetrance in female.

Typically, signs begin in the first or second decade of life, with attacks of flaccid paralysis. Classically, hypokalemia accompanies the attack, with or without associated electrocardiogram changes (increased PR and QT intervals, flattening of T waves, and prominent U waves). The attacks usually occur upon awakening at night or early in the morning. They are rarely observed by the physician, and must be suspected on the basis of clinical history.

Several triggers have been described, all acting through a lowering of serum potassium concentration: a carbohydrate load on the previous day, high salt intake, stress, certain medications (e.g., beta-agonists, corticosteroids, or insulin), and rest after strenuous exercise.

The frequency, length, and severity of the attacks are variable, but most often the attacks occur weekly to monthly, and can last up to several hours. Patients may variably report a prodrome consisting of paresthesias, fatigue, and behavioral or cognitive changes the day before the attack. Typically, patients regain full strength between attacks, and do not develop progressive myopathic features.

In hypokalemic periodic paralysis type 1, four mutations, implicating the α1 subunit of the skeletal muscle L-type calcium channel gene (CACN1AS) located on chromosome 1q, have been described, and account for the majority of cases.

In hypokalemic periodic paralysis type 2, more than five mutations of the α-subunit of the skeletal muscle sodium channel (SCN4A) gene on chromosome 17q in the voltage sensor have also been described, accounting for approximately 10% of cases. Certain authors think that these mutations give rise to a slightly different phenotype.

The nine mutations previously discussed in CACNA1S and SCN4A do not account for about one fifth to one third of patients with a clinical diagnosis of hypokalemic periodic paralysis, indicating additional possible allelic or genetic heterogeneity.

Therapeutics

The goal of treatment is to avoid attacks of weakness, or at least to decrease their frequency and severity.

Lifestyle modifications (i.e., avoidance of carbohydrate load, high salt intake, and strenuous exercise) are the first step in the management of these patients. Acute pharmacologic intervention consists of correcting the serum potassium level, which only treats indirectly the overt muscle weakness.

Chronic pharmacologic intervention consists of administering acetazolamide or dichlorphenamide, which are both carbonic anhydrase inhibitors. Anesthesia should be performed with caution because of the potential risk of pre- or postanesthetic weakness and malignant hyperthermia.

Prognosis

The prognosis is usually good, with the rare development of a proximal myopathy, which was found to develop independent of the actual frequency and severity of documented attacks.