[Current status of clinical and molecular-biological research on familial periodic paralysis]

Types of periodic paralysis seen in Japan are numerous: the one most frequently seen is hypokalemic periodic paralysis. Among them, approximately 50% are secondary to thyrotoxicosis. Number of families of familial hyperkalemic periodic paralysis have also been reported so far. Several cases of hyperkalemic periodic paralysis secondary to thyrotoxicosis have also been reported exclusively from Japan. As the pathogenesis of hypokalemic periodic paralysis, depolarization block induced by membrane permeability change in the face of hypokalemia triggered by excess insulin was strongly suggested and supported experimentally in part. Recent linkage analysis on familial hypokalemic periodic paralysis revealed that the abnormality is linked to a mutation in voltage-gated Ca channel. The difficulty remains how to explain the cause of hypokalemia which is almost always preceding the attack of periodic paralysis of this type. The cause of hyperkalemic periodic paralysis was shown to be the mutation in voltage-gated Na channel. Failure of inactivation of the channel causes an increase in inward sodium current which results in depolarization and accumulation of potassium. The explanation of the pathogenesis of paralysis is straight-forward when compared to that of hypokalemic periodic paralysis.