Life-Threatening Hypokalemia Revealing CACNA1S-Related Hypokalemic Periodic Paralysis

Familial hypokalemic periodic paralysis (HypoPP) is a rare autosomal dominant skeletal muscle channelopathy most commonly caused by pathogenic variants in the CACNA1S gene. It is characterized by recurrent episodes of severe hypokalemia and transient flaccid paralysis resulting from intracellular potassium redistribution rather than true potassium depletion. Despite advances in molecular genetics, familial HypoPP remains underrecognized, particularly in regions where acquired causes such as thyrotoxic periodic paralysis predominate. We report a young adult male presenting with recurrent episodes of severe hypokalemia complicated by cardiac conduction abnormalities and requiring intensive care management. A systematic diagnostic evaluation, including next-generation sequencing, was undertaken to exclude secondary and renal causes of hypokalemia. Genetic analysis identified a heterozygous pathogenic CACNA1S variant (c.1583G>A; p.Arg528His), confirming hypokalemic periodic paralysis type 1 (HypoPP1). This case highlights the importance of a structured diagnostic approach to recurrent hypokalemia and emphasizes the role of molecular testing in distinguishing familial channelopathies from more common acquired etiologies. We further discuss genotype-phenotype correlations, variable penetrance, implications for family screening, and emerging genotype-guided therapeutic strategies in hypokalemic periodic paralysis. The report underscores the growing importance of molecular diagnostics in the evaluation and management of rare neuromuscular channelopathies within the framework of contemporary precision medicine.