Genetic disorder involving ion channels of the cellular membrane and
affecting electrolyte conductance leading to episodic muscle weakness. It is
characterized by episodes of flaccid muscle weakness occuring at irregular intervals.
Most of the conditions are hereditary.
Familial Periodic Paralysis, Hypokalemia, Hyperkalemia, Myotonia,
Paramyotonia Congenita, Potassium-aggravated Myotonia; Becker Myotonia Congenita; Thomsen
Myotonia Congenita; Adynamia Episodica Hereditaria with or without Myotonia; Gamstorp
Disease; Thyrotoxic Periodic Paralysis.
Primary periodic paralysis can be classified according to
the membrane electrolyte defect:
Sodium Channel: Hyperkalemic PP; Paramyotonia Congenita; Potassium-aggravated myotonia
Calcium Channel: Hypokalemic PP; Thyrotoxic PP (secondary form)
Chloride Channel: Normokalemic PP; Becker Myotonia Congenita; Thomsen Myotonia Congenita
In the United States, the frequency for all forms of PP remains
unknown. Hypokalemic periodic paralysis form is the most common. It has a prevalence of 1
per 100,000 population. Becker myotonia congenita has a reported prevalence of 1 per 50,000, whereas Thomsen myotonia congenita seems significantly rarer.
Internationally, the incidence for this medical condition has not been established. Thyrotoxic periodic paralysis is more common in males (85%) of Asian
descent, leading to a frequency of approximately 2%.
All are autosomal dominant but penetrance
seems to be variable in female carriers. Hypokalemic periodic paralysis is
caused by a mutation in the alpha-1 unit of the dihydropyridine-sensitive
calcium channel CACNL1A3; the gene is located on chromosome 1q31-32.
Hyperkalemic periodic paralysis is caused by a mutation in the alpha subunit
of the Na channel SCN4A; the gene is located on chromosome 17q13.1-q13.3. It
is the same gene as paramyotonia congenita. The gene of normokalemic
periodic paralysis is still unknown—whether it is a separate entity or a
subgroup of the hyperkalemic form is a subject of debate.
The physiopathologic basis of flaccid muscle weakness is
inexcitability of the muscle membrane, i.e., the sarcolemma. In the hypokalemic form,
potassium (K) outflow is diminished by altered calcium homeostasis in the muscle fibers; in
the hyperkalemic form, the muscle fibers remain depolarized and their membranes are
Based on history, clinical examination, and measurement
of serum electrolytes during the attacks.
Hypokalemic form: Onset rarely occurs before the second decade of
life. Attacks of muscle weakness typically occur at night or in the early morning. They
are triggered by increased physical exercise, stress, cold, or a large carbohydrate
intake. Paralysis is flaccid, affects mainly the girdle of the lower limbs, and spares
the respiratory muscles as well as the muscles supplied by the cranial nerves. The attack
usually lasts 6 to 24 hours. ECG signs of hypokalemia can be observed. Treatment: Oral
KCl in case of attack but electrolytes should be monitored as rebound hyperkalemia is
frequent; prophylaxis with acetazolamide or spironolactone. Thyrotoxic periodic
paralysis is the most common hypokalemic PP. It is most common in adults 20-40
years of age. Hyperinsulinemia, carbohydrate load, and exercise may all cause PP ...