In patients with mutations in the genes that encode the
chloride,
sodium, and
calcium channels in skeletal muscle, there is abnormal function of the muscle membrane, which can cause
myotonia or attacks of weakness. Mutations in the
chloride and
sodium channels can lead to
myotonia, which typically begins in early childhood.
Mexiletine is usually effective in controlling
myotonia in these patients.
Mexiletine is also effective in preventing attacks of cold-provoked muscle
paralysis in patients with
paramyotonia congenita, a
sodium channel disorder. Certain mutations in the
sodium channel cause attacks of
hyperkalemic periodic paralysis; these attacks are often controlled with
thiazide diuretics. Mutations in the skeletal muscle
calcium channel cause periodic attacks of weakness, but
hypokalemia (not
hyperkalemia) occurs during these episodes. The
carbonic anhydrase inhibitors acetazolamide and
dichlorphenamide prevent attacks of
hypokalemic periodic paralysis, although the mechanism by which they produce this protective effect remains a mystery. Interestingly, the hypokalemic attacks with periodic weakness that occur in some thyrotoxic patients are made worse by
acetazolamide. This undesirable response to treatment emphasizes that not all disorders associated with
hypokalemic periodic paralysis will benefit from
carbonic anhydrase inhibitor therapy.
DNA analysis to search for a mutation in the genes that encode for
chloride,
sodium, or
calcium channels in skeletal muscle is helpful to establish the diagnosis. Some patients may eventually require provocative testing, however, to evaluate the attack of weakness and to reach a final diagnosis. Fortunately, there are effective treatments for the
channelopathies that affect the skeletal muscle membrane.