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 [1] [2] [3]. 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 [1]. 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 [1] [2] [3] [4]. 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 [1] [3]. 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 [1]. Moreover, many patients report injuries from falls during the attacks, a finding that can be quite debilitating on a long-term basis [5]. 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 [3] [4] [5]. Patients are asymptomatic between the attacks, whereas a minority of individuals suffers from progressive weakness [4].

• Chills

  Getting chilled is a trigger. Eating or drinking cold foods or beverages may provoke attacks in sensitive individuals. Weather changes seem to affect some HyperKPP patients adversely. [hkpp.org]

• Nausea

  Addison’s disease represents a raredisorder characterized by primary adrenal failure, general weakness, poor appetite, nausea, dizziness, and hyperpigmentation. [kci.go.kr]

  Addison`s disease represents a rare disorder characterized by primary adrenal failure, general weakness, poor appetite, nausea, dizziness, and hyperpigmentation. [happycampus.com]

  […] asymmetric Sphincters not involved Tendon reflexes: Reduced or Absent Systemic Thyrotoxicosis Usually symptomatic May be subclinical Family history: Common Cardiac arrhythmias: Sinus tachycardia commmon; Occasional ventricular tachycardia Weight loss Nausea [neuromuscular.wustl.edu]

• Tachycardia

  […] commmon; Occasional ventricular tachycardia Weight loss Nausea & Vomiting Difficulty with micturition Course: Resolves without morbidity after treatment of thyroid disease Laboratory Serum K + Usually: Hypokalemia: < 2.5 μmol/L May be severely reduced [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]

• Sweating

  Prodromal symptoms the day prior to an attack comprised fatigue, weakness, irritability, or restlessness (38.6%), with sweating, myalgia, stiffness, weakness, restlessness, tingling, and/or numbness more immediately preceding the attack (85.7%), usually [reliasmedia.com]

  With this form of PP, you may also have thyroid-related symptoms such as anxiety, sweating, weight loss, and anan abnormal sensation of the heartbeat (palpitations). [cedars-sinai.org]

  With this form of PP, you may also have thyroid-related symptoms such as anxiety, sweating, weight loss, and palpitations (an abnormal sensation of the heartbeat). Andersen-Tawil syndrome usually begins before age 18. [saintlukeskc.org]

  Hidrex Therapie About Hyperhidrosis Hyperhidrosis Videomicroscopic study ... of sweat expulsion Surgical Treatment of Hyperhidrosis - Videoscopic Surgery Center Excessive Sweating Surgical Treatment of Hyperhidrosis - Videoscopic Surgery Center Brief [catsclem.nl]

  These include prodromal paresthesias, sweating [12], post-ictal myalgia [14], post-ictal extreme fatigue, thirst, shortness of breath (either due to anxiety or to the episode itself), palpitations, clumsiness, irritability, and mental dullness. [translational-medicine.biomedcentral.com]

• 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]

  Muscle weakness during an attack usually affects the arms and legs and muscles of the eyes, throat, and trunk. Most often, these episodes involve a temporary inability to move muscles in the arms and legs. [rarediseases.info.nih.gov]

• Myopathy

  We studied four families with the latter disease in which some members developed a progressive myopathy. [ncbi.nlm.nih.gov]

  G72.1 알콜성 근병증(Alcoholic myopathy) G72.2 기타 독성물질에 의한 근병증(Myopathy due to other toxic agents) 독성물질감별을 원한다면 추가로 외인분류번호(XX장)를 사용할 것. [dic.impact.pe.kr]

  HyperKPP is one of a group of diseases, called inherited myopathies, that causes problems with the tone and contraction of skeletal muscles. [mda.org]

  G71.3 Mitochondrial myopathy, not elsewhere classified G71.8 Other primary disorders of muscles G71.9 Primary disorder of muscle, unspecified G72 Other and unspecified myopathies G72.0 Drug-induced myopathy G72.1 Alcoholic myopathy G72.2 Myopathy due [icd10data.com]

• Oliguria

  […] activity Carbohydrate-rich meal Cold Alcohol Less in later life, 40's and 50's Rhabdomyolysis CACNA1S mutations: R528H; R1086C; R1086H; R1239G; R1239H Other features associated with attack Myotonia: Not in limbs (Excludes diagnosis); Focal in eyelids Oliguria [neuromuscular.wustl.edu]

• Polyuria

  40's and 50's Rhabdomyolysis CACNA1S mutations: R528H; R1086C; R1086H; R1239G; R1239H Other features associated with attack Myotonia: Not in limbs (Excludes diagnosis); Focal in eyelids Oliguria Obstipation Diaphoresis After attack Muscle discomfort Polyuria [neuromuscular.wustl.edu]

• 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]

  […] disorders characterized by recurring attacks of rapidly progressive flaccid 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 [icd9data.com]

• Confusion

  In clinical studies, the most common side effects of Keveyis were a burning or pricking sensation, difficulty thinking and paying attention, changes in taste, and confusion. [ptcommunity.com]

  IMPORTANT SAFETY INFORMATION In clinical studies, the most common side effects of Keveyis were a burning or pricking sensation, difficulty thinking and paying attention, changes in taste, and confusion. [businesswire.com]

  In clinical studies, the most common side effects of KEVEYIS were a numbness or tingling, difficulty thinking and paying attention, changes in taste, and confusion. These are not all of the possible side effects that you may experience with KEVEYIS. [globenewswire.com]

  The term 'hyperkalemic' is somewhat confusing, because in most patients the level of potassium in the blood does not rise above normal during attacks. [hkpp.org]

• Paresthesia

  • 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]

  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]

• Stroke

  Collaborative Meta-Analysis of Randomised Trials of Antiplatelet Therapy for Prevention of Death, Myocardial Infarction, and Stroke in High Risk Patients. ‎ [books.google.es]

  National Institute of Neurological Disorders and Stroke. Published March 12, 2012. Accessed July 1, 2015. [2] inVentiv Health, United Health Claims Database Analysis, October 2014. [businesswire.com]

  […] identical to periodic paralysis and responsive to acetazolamide, with no recognized channelopathy mutation, but with mitochondrial DNA mutations previously associated with Leigh syndrome and MELAS (mitochondrial encephalopathy with lactic acidosis and stroke-like [reliasmedia.com]

  Patients develop highly progressive atherosclerosis that can lead to premature cardiovascular disease (stroke, coronary and peripheral artery disease. Patients expressing major hypertriglyceridemia may also develop acute pancreatitis. [orpha.net]

• Encephalopathy

  […] with acute episodes of limb weakness, identical to periodic paralysis and responsive to acetazolamide, with no recognized channelopathy mutation, but with mitochondrial DNA mutations previously associated with Leigh syndrome and MELAS (mitochondrial encephalopathy [reliasmedia.com]

  […] aciduria) & ↑ glycosuria Hypokalemia --> ↑ Digitalis toxicity c Arrhythmia or AV block Hydrochlorothiazide를 사용하는 환자: the severity of the hypokalemia c Hypomagnesemia ∝ ventricular Ectopy L.C : hypokalemia --> ↑ renal tubular ammonia--> aggrevate Hepatic encephalopathy [gall.dcinside.com]

  Oxygen Therapy HBO Medicine Overview HYPERBILIRUBINEMIE FYSIOLOGISCHE GEELZUCHT HYPERBILIRUBINEMIA Zie ook: GAL GALVLOEISTOF GALZOUTEN GALKLEURSTOF GROTE GALGANG BILE Zie ook: RODE BLOEDLICHAMEN ERYTHROCRYTEN Zie ook: BILIRUBINE ENCEFALOPATIE BILIRUBINE ENCEPHALOPATHY [catsclem.nl]

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 [5]. For this reason, the importance of a detailed patient history and a proper physical examination is perhaps of paramount importance [1]. 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 [1]. 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) [1] [2] [3]. 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 [1] [3].

• Hyponatremia

  Individuals studied included a female infant with failure to thrive, hyponatremia, and hyperkalemia; the infant's asymptomatic mother and father; and a maternal aunt and grandmother with hyperkalemic periodic paralysis. [ncbi.nlm.nih.gov]

• Electromyogram Abnormal

  Electrocardiogram and electromyogram abnormalities are also visible. In some cases, the anomalies result in cardiac arrhythmias. For the moment there is no effective treatment in 100% of cases. [testprenataleaurora.it]

• Peaking T Wave

  EKG change sequence: tall peaked T waves, diminished R waves amplitude, increased QRS or PR intervals and P wave disappearance. Slow infusion (over 5 min) of 10% calcium gluconate (reduces cardiac sensitivity to hyperkalemia). [hkpp.org]

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]

Treatment The goal of treatment is to relieve symptoms and prevent further attacks. Attacks are seldom severe enough to require emergency treatment. [pennstatehershey.adam.com]

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]

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]

Severe prognosis in a large family with hypokalemic periodic paralysis. Muscle Nerve. 2003;27:165–9. 13. Mutation analysis of two patients with hypokalemic periodic paralysis and suspected malignant hyperthermia. Muscle Nerve. 2004;30:114–7. [revistas.fucsalud.edu.co]

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]

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]

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]

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]

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]

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]

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]

(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]

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]

Prevention The medicines acetazolamide and thiazides prevent attacks in many cases. A low potassium, high carbohydrate diet, and light exercise may help prevent attacks. Avoiding fasting, strenuous activity, or cold temperatures also may help. [pennstatehershey.adam.com]

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]

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.