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 .
Jaw & Teeth
- Masseter Spasm
During surgery, avoid use of depolarizing anesthetic agents including suxamethonium and anticholinesterases that increase myotonia, which can result in masseter spasm and stiffness of respiratory and other skeletal muscles, and interfere with intubation [hkpp.org]
Prevention of secondary complications: During surgery, avoid use of depolarizing anesthetic agents (including potassium, suxamethonium, and anticholinesterases) that aggravate myotonia and can result in masseter spasm and stiffness of respiratory and [ncbi.nlm.nih.gov]
Increased Q-T interval (Early) Premature ventricular contractions Polymorphic ventricular tachycardia Heart block Long QT syndrome 7 Other EKG U waves: Prominent Semilunar valve abnormalities Treatment Amiodarone Poor response to classical therapy Cardiac [neuromuscular.wustl.edu]
SERUM POTASSIUM CONCENTRATION LOW NORMAL ECG U waves, flattening of T waves TACHYCARDIA 2nd or 3rd degree conduction block, QRS prolongation and T wave abnormality MUSCLE BIOPSY SINGLE OR MULTIPLE CENTRALLY PLACED VACUOLES NI/NORMAL NERVE CONDUCTION TEST [slideshare.net]
tachycardia, and ventricular bigeminy. [translational-medicine.biomedcentral.com]
Patients with hyperkalemia may experience a variety of dysrthymias including complete heart block, Mobitz type II second-degree atrioventricular block, ventricular tachycardia, ventricular fibrillation and asystole, muscle cramps, weakness, paralysis, [jpharmacol.com]
Hyperkalemia can cause cardiac arrhythmia, usually tachycardia, and typical ECG abnormalities (i.e., T-wave elevation, disappearance of P waves). Rest after exercise provokes weakness as in hyperPP. [ncbi.nlm.nih.gov]
- Muscle Weakness
But repeated attacks may lead to permanent muscle weakness. HyperPP responds well to treatment. Treatment may prevent, and may even reverse, progressive muscle weakness. [nlm.nih.gov]
All three had prominent fixed muscle weakness, while the remaining four did not. [ncbi.nlm.nih.gov]
Paroxysmal muscle weakness: the familial periodic paralyses. J Neurol. 2006 Nov;253(11):1391-8. Epub 2006 Nov 30. Review. [ghr.nlm.nih.gov]
We studied four families with the latter disease in which some members developed a progressive myopathy. [ncbi.nlm.nih.gov]
About one third may develop a chronic progressive myopathy. Hyperkalemic periodic paralysis is caused by mutations in the SCN4Agene and is inherited in an autosomal dominant manner. [rarediseases.info.nih.gov]
- Flaccid Paralysis
These procedures produced attacks of flaccid paralysis that occurred concomitantly with rapid rises in serum potassium concentrations and decreases in blood glucose and inorganic phosphate levels. [ncbi.nlm.nih.gov]
CASE REPORT An 11-year-old girl presented to the emergency room with flaccid paralysis of the lower extremities, to the point where she could neither walk nor sit up in bed.1 Symptoms had begun one hour earlier. [neurologytimes.com]
paralysis or myotonia; these conditions have in common a mutation of the gene encoding the alpha subunit of the sodium channel in skeletal muscle; frequently associated with fluctuations in serum potassium levels; periodic paralysis may also occur as [icd9data.com]
In some individuals, paresthesias, probably induced by the hyperkalemia, herald the weakness. During an attack of weakness, the muscle stretch reflexes are abnormally diminished or absent. [ncbi.nlm.nih.gov]
• Paresthesias often precede the onset of weakness by 1 or more days. Often gait ataxia with distal limb paresthesias. Pain, temp relatively spared. • At presentation half have some facial weakness • Ophthalmoparesis see in 10-20% of patients. [slideshare.net]
Others complain of paresthesias and cognitive impairment (described by patients as mental dullness, fogginess, inability to concentrate, or confusion) from acetazolamide. [translational-medicine.biomedcentral.com]
Patients with hyperkalemia may experience a variety of dysrthymias including complete heart block, Mobitz type II second-degree atrioventricular block, ventricular tachycardia, ventricular fibrillation and asystole, muscle cramps, weakness, paralysis, paresthesias [jpharmacol.com]
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  .
Other Test Results
He rapidly recovered from weakness after acetazolamide treatment. Magnetic resonance imaging of thighs comparing pre- and post-treatment revealed a significant increase in muscle bulk. [ncbi.nlm.nih.gov]
HyperPP responds well to treatment. Treatment may prevent, and may even reverse, progressive muscle weakness. [nlm.nih.gov]
Antenatal diagnosis Prenatal diagnosis is theoretically possible if the disease-causing mutation in the family has been identified but is rarely performed because of the non life-threatening prognosis. [orpha.net]
Outlook (Prognosis) Sometimes, attacks disappear later in life on their own. But repeated attacks may lead to permanent muscle weakness. Hyperkalemic periodic paralysis responds well to treatment. [coordinatedhealth.com]
Outlook (Prognosis) Sometimes, attacks disappear later in life on their own. But repeated attacks may lead to permanent muscle weakness. HyperPP responds well to treatment. Treatment may prevent, and may even reverse, progressive muscle weakness. [leehealth.org]
Family history Timing Intensity History of administration of certain drugs Clinical examination Differential Diagnosis Laboratory investigations Serum K CPK and serum myoglobin ECG EMG Nerve conduction studies Provocative Testing Muscle biopsy Treatment Prognosis [slideshare.net]
To investigate the role of this gene in the etiology of PC, a linkage analysis in 17 well-defined families was carried out. [ncbi.nlm.nih.gov]
Etiology HyperPP is a sodium muscle channelopathy due to point mutations (Thr704Met and Met1592Val mutations in 80% of cases) in the SCN4A gene encoding the alpha subunit of the skeletal muscle voltage-gated sodium channel Nav1.4. [orpha.net]
Hyperkalemic Periodic Paralysis Etiology: mutations in sodium channel NaV1.4 Precipitated By: hyperkalemia, potassium-rich meal, rest after exercise, stressful situations, possibly hypoglycemia Anesthesia Management: avoid cholinesterase inhibitors, SCh [openanesthesia.org]
Familial periodic paralysis is a disease of unknown etiology characterized by recurrent acute attacks of weakness associated with a fall in serum potassium levels. [jamanetwork.com]
Summary Epidemiology The prevalence is estimated at around 1/200,000. Clinical description Attacks of muscle weakness generally begin during childhood (first decade). [orpha.net]
To better define — or refute — previously accepted epidemiological, clinical, diagnostic, and therapeutic aspects of hyperPP, review of a large cohort of genetically confirmed cases was undertaken. [reliasmedia.com]
Home, Search, Index, Links, Pathology, Molecules, Syndromes, Muscle, NMJ, Nerve, Spinal, Ataxia, Antibody & Biopsy, Patient Info EPISODIC MUSCLE WEAKNESS Hypokalemic Periodic Paralysis Hypokalemic periodic paralysis, Hereditary: General features Epidemiology [neuromuscular.wustl.edu]
(including hypokalemic periodic paralysis and thyrotoxic periodic paralysis, and other “Channelopathies” or “Membranopathies) Pathophysiology Epidemiology Primary or familial periodic paralysis Secondary periodic paralysis Conventional classification [slideshare.net]
The pathophysiological mechanism is still unknown. Pathophysiological studies suggest that in this disorder the kidney lacks sensitivity to atrial natriuretic peptide. [ncbi.nlm.nih.gov]
The proposed study will investigate the pathophysiology of these diseases by (1) analyzing electrophysiological properties of mutant Na channel expressed in a myogenic cell line and (2) evaluating the physiological consequences of over-expressed wild [grantome.com]
Acta Paediatr Stockholm (Suppl) 108:1–126 Google Scholar Lehmann-Horn F, Iaizzo PA (1990) Resealed fiber segments for the study of the pathophysiology of human skeletal muscle. [link.springer.com]
Br J Anaesth 1980; 52: 153–64Ellis, FR Miller J, Katz RL: Muscle diseases, Anesthesia and Uncommon Disease: Pathophysiologic and Clinical Correlations, 2nd edition. Edited by Katz J, Benumof J, Kadis LB. [anesthesiology.pubs.asahq.org]
Treatment may prevent, and may even reverse, progressive muscle weakness. [nlm.nih.gov]
In a patient with hyperkalemic periodic paralysis, metaproterenol prevented muscular weakness and hyperkalemia in periods of rest after exercise. [ncbi.nlm.nih.gov]
To prevent the muscle from being perpetually contracted, the channel contains a fast inactivation gate that plugs the sodium pore very quickly after it opens. This prevents further entry of sodium. [en.wikipedia.org]
Prevention A medicine called acetazolamide prevents attacks in many cases. Other medicines may also be prescribed. A low potassium, high carbohydrate diet may help prevent attacks. [coordinatedhealth.com]
- Charles G, Zheng C, Lehmann-Horn F, Jurkat-Rott K, Levitt J. Characterization of hyperkalemic periodic paralysis: a survey of genetically diagnosed individuals. J Neurol. 2013;260(10):2606-2613.
- Han J-Y, Kim J-B. Familial hyperkalemic periodic paralysis caused by a de novo mutation in the sodium channel gene SCN4A. Korean J Pediatr. 2011;54(11):470-472.
- Patangi SO, Garner M, Powell H. Management of a patient with hyperkalemic periodic paralysis requiring coronary artery bypass grafts. Ann Card Anaesth. 2012;15(4):302-304.
- Lee YH, Lee H-S, Lee HE, et al. Whole-Body Muscle MRI in Patients with Hyperkalemic Periodic Paralysis Carrying the SCN4A Mutation T704M: Evidence for Chronic Progressive Myopathy with Selective Muscle Involvement. J Clin Neurol. 2015;11(4):331-338.
- Cavel-Greant D, Lehmann-Horn F, Jurkat-Rott K. The impact of permanent muscle weakness on quality of life in periodic paralysis: a survey of 66 patients. Acta Myol. 2012;31(2):126-133.