Abrupt hypokalemia with paralysis from a clinician?s perspective

Abstract

Monogenic hypokalemic periodic paralysis (HypoPP) is an autosomal dominant genetic disease. HypoPP is more common in males than females and has a reduced penetrance in females. Attacks generally begin during adolescence. They are aggravated by exercise, sleep, stress, alcohol, and meals rich in carbohydrates and salt. The episodes last 324h. Attacks often feature a prodrome of stiffness or heaviness in the lower extremities. Some patients report that they can abort their attacks with mild exercise. Various preventive measures have been suggested, including a low-carbohydrate, low sodium diet, acetazolamide, dichlorphenamide, spironolactone, and triamterene, though none of these are very effective. Acute attacks are generally treated with potassium every 30min until strength returns. In patients with severe episodes who also experience gastrointestinal symptoms, parenteral potassium may be necessary. The electrocardiogram should also be monitored. The paralysis is due to abnormal muscle membrane excitability, commonly arising from mutations in the muscle calcium channel alpha1 subunit gene (CACNA1S) on chromosome 1q3132 or in a smaller number of cases, from a mutation in the skeletal muscle sodium channel SCN4A. The alpha1 subunit of the calcium channel contains the dihydropyridine binding site (receptor) that acts as a pore for conducting calcium ions in the T tubule. The mutation results in a reduction of the calcium current in the T tubule. During attacks, there is an influx of potassium into muscle cells and the cells become electrically refractile. The patients have an increased sensitivity to insulin-related effects on potassium. Exactly how the potassium is shifted from the extracellular to the intracellular space as a result of impaired function of the calcium channel dihydropyridine receptor is not entirely clear.