Clinical meaning
Hyperkalemic periodic paralysis (HyperPP) is an autosomal dominant channelopathy caused by gain-of-function mutations in the SCN4A gene encoding the alpha subunit of the skeletal muscle voltage-gated sodium channel (Nav1.4). The mutant channels fail to inactivate properly, causing persistent sodium influx that initially depolarizes the muscle membrane (causing myotonia — sustained muscle contraction) but eventually leads to sustained depolarization that inactivates sodium channels, rendering the muscle inexcitable (flaccid paralysis). Episodes are triggered by: elevated serum potassium (potassium-rich meals, fasting, rest after exercise, cold exposure, stress). Unlike hypokalemic periodic paralysis, potassium is elevated (or high-normal) during attacks. Episodes typically begin in the first decade of life, last 15 minutes to a few hours (shorter than hypokalemic attacks), and are milder. Between attacks, examination may show myotonia (delayed muscle relaxation after contraction — percussion myotonia, grip myotonia). Diagnosis is confirmed by genetic testing for SCN4A mutations. EMG during attacks shows decreased compound muscle action potential (CMAP) amplitude. Acute treatment: mild exercise may abort early attacks; inhaled albuterol (beta-2 agonist drives K+ intracellularly); IV calcium gluconate for severe attacks with significant hyperkalemia. Prevention: avoid triggers (potassium-rich foods, fasting, cold); acetazolamide or dichlorphenamide (carbonic anhydrase inhibitors — mechanism unclear, may stabilize pH and membrane potential); thiazide diuretics (promote renal K+ excretion).