Hypokalemic Periodic Paralysis

Pediatrics in Review

Volume 18 Number 10 October 1997
Copyright 1997 American Academy of Pediatrics

This section of Pediatrics in Review reminds clinicians of those conditions that can present in a misleading fashion and require suspicion for early diagnosis. Emphasis has been placed on conditions in which early diagnosis is important and that the general pediatrician might be expected to encounter, at least once in a while.

Case 3 Presentation

A 16 year-old boy is referred to the emergency department for evaluation of generalized weakness. He reports that 2 days ago, following 2 days of “flu-like” symptoms, he became weak while climbing stairs. His weakness progressed rapidly; soon he was unable to move his extremities or sit up. His mother has helped him eat, drink, and urinate. He uses no medications, alcohol, or illicit drugs. He has no history of ingestions, fever, dyspnea, dysphagia, or paresthesias. He had a similar episode of weakness 4 years ago that was less severe and resolved spontaneously within 2 days. His grandmother has had similar episodes.

The physical examination reveals an alert, welldeveloped young man who has normal vital signs. He cannot support himself sitting or standing and has no ability to support, flex, or extend his neck. He is areflexic and has flaccid paralysis of his trunk and proximal extremities. His grasp is mildly myotonic and limited to his index fingers and thumbs. He can wiggle his toes and plantar flex (4/5). Cranial nerves II through XII are intact, as is sensation to light touch, pin prick, proprioception, and vibration. The remainder of his examination is normal except for the absence of bowel sounds.

A single laboratory test reveals the etiology of his weakness and suggests the diagnosis.

Case 3 Discussion

This boy’s serum potassium was 1.4 mEq/L (on repeat determination, 1.5 mEq/L); other electrolyte levels were normal. Several of his signs and symptoms were consistent with severe hypokalemia: muscle weakness, flaccid paralysis, hyporeflexia, decreased peristalsis/ileus, apathy, and lethargy. Other signs of severe hypokalemia include paresthesias, confusion, respiratory depression, and arrhythmias. This patient’s electrocardiogram also revealed abnormalities often seen with hypokalemia: low-voltage T waves, the appearance of prominent U waves, ST segment depression, and a prolonged QT interval. Patients who have hypokalemia are at risk for cardiac arrhythmias, including premature ventricular contractions, atrial or nodal tachycardia, ventricular tachycardia, and ventricular fibrillation.

The patient’s history of a similar previous episode of weakness, his age and gender, and the documented hypokalemia during his current episode of weakness suggest the diagnosis of hypokalemic periodic paralysis.

The periodic paralyses constitute a group of disorders involving episodic attacks of weakness in the absence of rapidly identifiable causes of hypokalemia, such as gastroenteritis, intestinal obstruction, renal tubular acidosis, hyperaldosteronism, and other conditions. Three forms of this condition are outlined in the Table below. Patients who have the hypokalemic form exhibit significant hypokalemia during their episodic attacks of weakness. Two thirds of the cases are inherited in an autosomal dominant pattern; one third are sporadic. Males are affected more frequently and more severely. The attacks begin in the first 3 decades of life, typically in early adolescence. The frequency of attacks may vary from daily to yearly. An attack can last from 4 to more than 24 hours. The attacks typically follow rest or sleep, but may occur after exercise.

TABLE – Forms of Primary Familial Periodic Paralysis
Potassium level Low High Normal
Inheritance Autosomal dominant: High penetrance in males Autosomal dominant
Gene locus lq32 17q23.1-25.3
Mutation Alpha1 subunit of dihydropyridine-sensitive calcium channel Alpha1 subunit of tetrodotoxin-sensitive sodium channel

*Hyperkalemic periodic paralysis is associated not only with episodic weakness but also with myotonia, particularly of the tongue and periorbital musculature.

**Normokalemic periodic paralysis may be a variant of hyperkalemic periodic paralysis.

The attacks are characterized by weakness and subsequent paralysis of the limb muscles; proximal muscles are affected more often than distal ones. The ocular, bulbar, and respiratory muscles rarely are involved. During the attacks, patients are alert but hyporeflexic. They are at risk for cardiac arrhythmias at these times. The attacks can be fatal if the bulbar or respiratory muscles are involved. Initially, patients regain normal function between attacks, but multiple attacks over several years eventually lead to progressive proximal weakness.

The pathogenesis of hypokalemic periodic paralysis is incompletely understood. It is thought to be related to an abnormality in the muscle membrane that leads to an excessive flux of potassium from the blood into the muscles.

The diagnosis is made most easily when hypokalemia is documented during an attack of weakness and other secondary causes of hypokalemia are excluded. This patient had no history of gastrointestinal or renal losses of potassium. His other serum electrolytes, including magnesium, as well as his urinary potassium excretion were normal. There was no acidosis (excluding the possibility of renal tubular acidosis) or alkalosis (excluding Bartter syndrome). He was not hypertensive, excluding the possibility of hyperaldosteronism or glucocorticoid excess. There were no other causes of cellular shifts leading to hypokalemia, such as alkalosis, insulin use, or beta-adrenergic catecholamine use. This patient’s history of a prior episode of weakness, his current episode of weakness with documented hypokalemia, his grandmother’s history of episodic weakness, and the exclusion of other causes of hypokalemia confirm the diagnosis.

When evaluating an individual who has an episode of paralysis associated with low serum potassium, thyroid function tests should be obtained because there is a form of thyrotoxic periodic paralysis associated with hypokalemia. This patient had normal thyroid function tests.

The acute management of patients during these attacks is repletion with oral potassium, 0.2 to 0.4 mmol/kg, every 30 minutes. Intravenous potassium is not recommended because it can lead to additional cellular shifts and temporarily decrease potassium levels further. The patient should be on a cardiac monitor and have serial electrocardiograms taken. This patient slowly regained movement and strength as his serum potassium level increased. Findings on physical examination were normal within 24 hours.

The longterm management of hypokalemic periodic paralysis involves prevention of attacks through the use of acetazolamide, a carbonic-anhydrase inhibitor. The mechanism of this therapy is not understood fully, but may be related to prevention of the flux of potassium from the blood to the muscle. Supplemental potassium does not prevent attacks. Hypokalemic periodic paralysis is a rare disease, but should be included in the differential diagnosis of any patient younger than 30 years of age who suffers episodic attacks of weakness. ( Kathryn Wiseman, MD, University of Rochester School of Medicine and Dentistry, Rochester, NY; Gregory P. Conners, M.D., University of Rochester School of Medicine and Dentistry, Rochester, NY.)

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