Periodic paralyses: when channels go wrong.

In 1865, Claude Bernard wrote that ‘the constancy of the internal milieu is the essential condition to a free and independent life’ [1]. It would be hard to find a more illustrative paradigm for that statement than for the case of hyperkalaemic periodic paralysis (HyperPP) reported by Grgic et al. in this issue [2]. A 14-year-old male was admitted for a sudden ascending paralysis involving the four limbs that appeared shortly after exercise. The symptoms were associated with a severe hyperkalaemia (6.3 mmol/L). Remarkably, both the muscle strength and the K+ level normalized spontaneously within 2 h. Since the patient had presented similar episodes since childhood, a clinical diagnosis of HyperPP was made, later confirmed by provocation with exercise and oral K+ intake. Genetic analysis detected a known mutation (T704M) in the SCN4A gene that encodes the α subunit of the Nav1.4 voltage-gated sodium channel. The mutation was not detected in the biological parents of the proband. This case is relevant for K+ homeostasis, Na+ channelopathies and genotype–phenotype correlations.