Hyperkalemic periodic paralysis is a rare genetic disorder in which mutations of proteins encoding sodium channels cause sudden attacks of muscle weakness and a variable degree of paralysis that start in the first decade of life. The diagnosis can be difficult to make in the absence of a meticulous clinical and laboratory workup, including provocative tests, electromyography, muscle magnetic resonance imaging and genetic studies.
Hyperkalemic periodic paralysis is an autosomal dominant genetic disease that stems from mutations in the skeletal muscle sodium voltage-gated channel (specifically the alpha subunit 4, or the SCN4A gene) that leads to disruption of normal ion exchange   . Although the condition is considered to be quite rare (affecting approximately 1 in 200,000 individuals), its early recognition is vital in reducing the grave disability that is imposed on the individuals . Signs and symptoms arise during the first decade of life in virtually all patients, and the sudden onset of reversible flaccid muscle weakness (or even paralysis) that last from minutes up to several hours is the hallmark of this condition, although certain studies report that attacks may last for even days    . Attacks develop as a result of increased serum potassium levels. Consequently, events that cause an increase in serum potassium - hypothermia, fasting, emotional stress, potassium-rich foods, as well as strenuous exercise, are recognized triggers  . Additional signs include focal weakness, areflexia of the affected muscles during the attacks (predominantly the calf and the thighs), and preservation of the sensorium and sphincter control, while myotonia may be seen as well . Moreover, many patients report injuries from falls during the attacks, a finding that can be quite debilitating on a long-term basis . Attacks seem to be most frequently reported during the morning, before breakfast, and their appearance peaks during adolescence, after which they gradually subside in adulthood, but persist throughout life   . Patients are asymptomatic between the attacks, whereas a minority of individuals suffers from progressive weakness .
The diagnosis of hyperkalemic periodic paralysis may not be easy to make, but its life-long disability and marked impairment of the quality of life mandate early recognition of the disorder. Furthermore, studies have confirmed that the diagnosis is made approximately 26 years after symptoms have appeared, emphasizing the pivotal role of clinical suspicion toward hyperkalemic periodic paralysis . For this reason, the importance of a detailed patient history and a proper physical examination is perhaps of paramount importance . The age of onset, appearance, and course of symptoms should be noted, while information regarding recent complaints within the close family (parents, grandparents, siblings) must be evaluated as well during the interview . On the other hand, a meticulous neurological and muscle examination, especially during the attacks, can provide key findings in order to pursue the diagnosis of hyperkalemic periodic paralysis. Several diagnostic tests are used to solidify the diagnosis, including electromyography (EMG) that will show signs of myotonia in 50% of cases, provocative testing in the form of potassium challenge test, muscle biopsy and muscle magnetic resonance imaging (MRI)   . Genetic testing for SCN4A mutations, although positive in only 60% of cases with evident clinical criteria, is a definite tool to confirm hyperkalemic periodic paralysis  .