Hyperkalemic periodic paralysis

Hyperkalemic periodic paralysis (HyperKPP), also known as hyperkalemic periodic paralysis type 1 or Gamstorp disease, is a rare inherited neuromuscular disorder characterized by episodes of muscle weakness or paralysis associated with elevated serum potassium levels. The condition is caused primarily by mutations in the SCN4A gene, which encodes the alpha subunit of the skeletal muscle voltage-gated sodium channel (Nav1.4). These mutations lead to abnormal sodium channel function, resulting in sustained muscle fiber depolarization and impaired muscle excitability. The skeletal muscular system is primarily affected, though cardiac complications related to hyperkalemia can occasionally occur. Episodes of weakness typically begin in the first or second decade of life and are often triggered by rest after exercise, fasting, cold exposure, emotional stress, or potassium-rich foods. Attacks usually last from minutes to several hours and tend to be shorter and more frequent than those seen in hypokalemic periodic paralysis. Weakness most commonly affects the limbs, particularly the proximal muscles, though respiratory muscles are usually spared. Many patients also experience myotonia (muscle stiffness), which may be present between attacks. Over time, some individuals develop a progressive fixed myopathy with permanent muscle weakness, particularly in the lower extremities. Treatment focuses on preventing and managing acute episodes. Acute attacks may be managed by mild exercise, ingestion of carbohydrates, or inhaled beta-adrenergic agonists such as salbutamol to help lower serum potassium. Preventive strategies include avoiding known triggers and dietary potassium restriction. Medications such as thiazide diuretics, acetazolamide, or dichlorphenamide (a carbonic anhydrase inhibitor approved by the FDA for periodic paralysis) may be used prophylactically to reduce attack frequency and severity. Regular monitoring for the development of permanent myopathy and cardiac rhythm disturbances is recommended.

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