Periodic paralysis.
Periodic paralyses are rare diseases characterized by severe episodes of muscle weakness concomitant to variations in blood potassium levels. It is thus usual to differentiate hypokalemic, normokalemic, and hyperkalemic periodic paralysis. Except for thyrotoxic hypokalemic periodic paralysis and periodic paralyses secondary to permanent changes of blood potassium levels, all of these diseases are of genetic origin, transmitted with an autosomal-dominant mode of inheritance. Periodic paralyses are channelopathies, that is, diseases caused by mutations in genes encoding ion channels. The culprit genes encode for potassium, calcium, and sodium channels. Mutations of the potassium and calcium channel genes cause periodic paralysis of the same type (Andersen-Tawil syndrome or hypokalemic periodic paralysis). In contrast, distinct mutations in the muscle sodium channel gene are responsible for all different types of periodic paralyses (hyper-, normo-, and hypokalemic). The physiological consequences of the mutations have been studied by patch-clamp techniques and electromyography (EMG). Globally speaking, ion channel mutations modify the cycle of muscle membrane excitability which results in a loss of function (paralysis). Clinical physiological studies using EMG have shown a good correlation between symptoms and EMG parameters, enabling the description of patterns that greatly enhance molecular diagnosis accuracy. The understanding of the genetics and pathophysiology of periodic paralysis has contributed to refine and rationalize therapeutic intervention and will be without doubts the basis of further advances.
Fontaine
Bertrand
B
INSERM, UMR 546, Paris, France; Université Pierre et Marie Curie-Paris 6, UMR S546 and Assistance Publique-Hôpitaux de Paris, Centre de référence des canalopathies musculaires, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
D006801:Humans; D020514:Hypokalemic Periodic Paralysis / Q000235:genetics / Q000628:therapy; D007473:Ion Channels / Q000235:genetics; D009132:Muscles / Q000378:metabolism / Q000473:pathology; D009154:Mutation / Q000235:genetics; D010245:Paralyses, Familial Periodic / Q000235:genetics* / Q000628:therapy; D020513:Paralysis, Hyperkalemic Periodic / Q000235:genetics / Q000628:therapy
D007473:Ion Channels