Chapter 1 - Sodium and calcium channelopathies of sarcolemma: Periodic paralyses, paramyotonia congenita and potassium-aggravated myotonia

Abstract

Periodic paralyses (PP), paramyotonia congenital (PC), and potassium aggravated myotonia (PAM) are inherited muscle disorders caused by mutation in genes encoding voltage-gated sodium or calcium channels. This chapter provides an overview of clinical features, genetics, pathogenesis, diagnosis, and therapy of the sodium and calcium channelopathies of sarcolemma— i.e., PP (both HyperPP and HypoPP), PC, and PAM. Three sodium channel diseases, hyperkalemic periodic paralysis (HyperPP), PC, and PAM are caused by mutations in the α-subunit of the human skeletal muscle sodium channel, whereas in hypokalemic periodic paralysis (HypoPP) mutations in the α-subunit of the L-type human skeletal muscle calcium channel are found. HyperPP is transmitted as an autosomal dominant trait with complete penetrance. The clinical phenotype of HyperPP is transient episode of muscle weakness or paralysis, often provoked by rest after exercise or by ingestion of potassium-rich food. Potassium loading, cold environment, emotional stress, glucocorticoids, and pregnancy provoke or worsen the attacks. HypoPP is transmitted as an autosmal dominant trait with reduced penetrance in women. The clinical phenotype of HypoPp paralytic attacks is associated with decrease of serum potassium. The major symptoms of HypoPP are on average of longer duration than in HyperPP. The clinical phenotype of PAM is muscle stiffness induced or aggravated by depolarizing agents such as potassium, which is without weakness or cold-sensitivity. The following are the clinical features manifested in PC: paradoxical myotonia, defined as muscle stiffness increasing with continued activity; severe worsening of the myotonia by cold; and weakness after long exposure to cold. This condition is transmitted as a dominant trait with complete penetrance.