Successful treatment of normokalemic periodic paralysis with hydrochlorothiazide

Abstract Background Periodic paralysis (PP) is an autosomal dominant muscle disorder characterized by periodic muscle weakness attacks associated with serum potassium level variations. It is classified into hypokalemic (hypoKPP), hyperkalemic (hyperKPP), and normokalemic (normoKPP) forms based on the ictal serum potassium level. HyperKPP and normoKPP are caused by mutations of the same gene SCN4A , the gene encoding the skeletal muscle voltage-gated sodium channel. Prophylactic treatment with thiazide diuretics is highly effective in preventing attacks in hyperKPP. However, the efficacy and safety of such diuretics in normoKPP remain unclear. Case We describe a familial case of normoKPP wherein the affected individuals showed periodic muscle weakness attacks, with an early childhood onset, and a lack of serum potassium level variation during the paralytic attacks. Sequencing analysis of SCN4A gene revealed a heterozygous missense mutation (c. 2111C > T, p. Thr704Met) in all symptomatic family members. Oral administration of hydrochlorothiazide, a thiazide diuretic, markedly improved the paralytic attack frequency and duration in the affected individuals without adverse effects. Conclusion Our case demonstrates the efficacy of hydrochlorothiazide in the prophylactic treatment of normoKPP caused by the SCN4A mutation of p.Thr704Met, the most frequent mutation of hyperKPP.