Topic:Hyperkalemic Periodic Paralysis
Hyperkalemic Periodic Paralysis (HYPP) is a genetic disorder affecting the skeletal muscles of horses, characterized by episodes of muscle weakness or paralysis. It is caused by a mutation in the gene responsible for encoding a sodium channel in muscle cells, which leads to abnormal muscle cell membrane excitability. This condition is predominantly observed in certain lines of Quarter Horses and related breeds. Clinical signs of HYPP can range from mild muscle twitching to severe paralysis, and episodes can be triggered by factors such as stress or dietary changes. This page compiles peer-reviewed research studies and scholarly articles that explore the genetic basis, pathophysiology, clinical presentation, and management strategies for Hyperkalemic Periodic Paralysis in horses.
Prophylactic efficacy of phenytoin, acetazolamide and hydrochlorothiazide in horses with hyperkalaemic periodic paralysis. Horses with hyperkalaemic periodic paralysis were challenged with an oral dose of potassium chloride, and the prophylactic efficacy of phenytoin, acetazolamide and hydrochlorothiazide was evaluated, with at least three weeks separating the trials of each drug. After the administration of potassium chloride without prophylactic medication the horses' clinical signs ranged from generalised fine muscle fasciculations to gross tremors, and weakness with occassional prolapse of the nictitating membrane; plasma potassium concentration increased significantly (P < 0.01) from 4.0 +/- 0.2 to 6.0 +/-...
Hyperkalaemic periodic paralysis in Australian quarter horses. Three Quarter Horse stallions and 5 of their 11 tested progeny were diagnosed as affected with the inherited autosomal dominant defect hyperkalaemic periodic paralysis in Victoria in 1992. The diagnoses were based on the appearance of clinical signs and associated increased plasma potassium concentrations in response to oral potassium loading. All affected horses were descendants of the American Quarter Horse Impressive. Indirect evidence indicates that at least 3 other affected Quarter Horse stallions have stood or are standing at stud in Australia. The clinical details of the affected horses...
Effect of phenytoin on skeletal muscle from quarter horses with hyperkalaemic periodic paralysis. The contractile activity, the threshold for calcium-induced calcium release in fractions of sarcoplasmic reticulum and the potassium concentration were determined in preparations of semimembranosus muscle from normal quarter horses and quarter horses with hyperkalaemic periodic paralysis before and after they were treated with phenytoin. Before the treatment there was no difference in caffeine contracture or electrically elicited twitch response between the two groups. For one week after the treatment, the time to peak tension of caffeine contractures was significantly (P < 0.005) reduced i...
Sodium channel inactivation is impaired in equine hyperkalemic periodic paralysis. 1. Equine hyperkalemic periodic paralysis (E-HPP) is a dominantly inherited disorder of muscle that causes recurrent episodes of stiffness (myotonia) and weakness in association with elevated serum K+. Affected horses carry a mutant allele of the skeletal muscle isoform of the Na channel alpha-subunit. To understand how this mutation may cause the disease phenotype, the functional defect in Na channel behavior was defined physiologically by recording unitary currents from cell-attached patches on normal and affected equine myotubes. 2. The presence of the mutation was confirmed in our cell lin...
[American Quarter Horses and HYPP]. Hyperkalaemic periodic paralysis is a genetic disease that affects the American Quarter Horse population and is caused by a mutation. As a result of this mutation in a gene which codes for the sodium channel in muscle cells, severe muscle weakness can appear. Reliable DNA-tests can establish whether a horse is homozygous negative, heterozygous, or homozygous positive for this mutation. Therapy and prevention are discussed.
Pathophysiology of sodium channelopathies: correlation of normal/mutant mRNA ratios with clinical phenotype in dominantly inherited periodic paralysis. It is often suggested that polygenic or environmental factors are responsible for clinical variability between patients with identical mutations. However, most dominant diseases are caused by a change-of-function alteration in the mutant allele's protein product. All patients are heterozygous and presumably express both mutant and normal proteins from the corresponding genes. Thus, a possible molecular mechanism for clinical variability could be the difference in relative levels of mutant vs. normal mRNA in different patients with the same mutation. To investigate this hypothesis, it is necess...
Equine hyperkalemic periodic paralysis: review and implications. The purpose of this review is to present an up-to-date summary of the signs, diagnosis, treatment, and implications of equine hyperkalemic periodic paralysis. The review encompasses all original articles published between 1986 and early 1993. Hyperkalemic periodic paralysis is the result of a genetic mutation in the skeletal muscle sodium channel gene. It is inherited as an autosomal dominant trait; most affected horses are heterozygotes. The classical signs are muscle fasciculation, spasm, and weakness associated with hyperkalemia. However, these signs are only rarely observed in affected hor...
Selection of quarter horses affected with hyperkalemic periodic paralysis by show judges. Thirty offspring of a Quarter Horse sire, affected by hyperkalemic periodic paralysis (HPP), were examined electromyographically. On the basis of the detection of or lack of spontaneous activity with high frequency myotonic or pseudomyotonic discharges, the horses were diagnosed as being affected (14 horses) or unaffected (16 horses) with HPP. The show performance of these horses was evaluated for the first 3 to 9 years of their life by use of American Quarter Horse Association records. Horses affected with HPP performed significantly (P < 0.01) better in halter classes than did unaffected ...
[HYPP–hyperkalemic periodic paralysis in horses]. A literature review of the clinical syndrome HYPP (Hyperkalemic periodic paralysis) affecting Quarter Horses is given. HYPP is characterized by sporadic attacks of muscle tremors, weakness and/or collapse, lasting for variable periods of time. Diagnosis is based on physical findings in association with hyperkalemia. In horses with HYPP, the regulation of ion transport through the sodium channels in the muscle cells occasionally fails, causing uncontrollable muscle twitching. Further investigations into molecular genetics reveals a mutation in the gene responsible for sodium and potassium regul...
Possible normokalemic variant of hyperkalemic periodic paralysis in two horses. Hyperkalemic periodic paralysis (HPP), characterized by intermittent episodes of muscle fasciculations, profound muscle weakness, and hyperkalemia, has been described in Quarter Horses, Appaloosas, and Paints. In previous reports, the hallmark of this syndrome has been the development of hyperkalemia during each episode. Two affected horses had episodes of paralysis without associated hyperkalemia, demonstrating that normokalemia during an episode otherwise consistent with HPP does not eliminate HPP as a diagnosis. This clinical presentation appeared to be a variant of HPP.
Phenytoin increases specific triacylglycerol fatty esters in skeletal muscle from horses with hyperkalemic periodic paralysis. Previous studies have demonstrated that phenytoin decreases the levels of triacylglycerols in several tissues other than skeletal muscle. Since phenytoin is clinically effective in several skeletal muscle disorders, triacylglycerol metabolism in skeletal muscle from four normal Quarter horses and four Quarter horses with hyperkalemic periodic paralysis was examined. The horses with hyperkalemic periodic paralysis had low levels of 18:3 in the phospholipids, low levels of 16:0, 16:1 and 18:3 in the free fatty acids and low levels of 20:4 in triacylglycerols. Triacylglycerol levels were increase...
[3H]ouabain binding in skeletal muscle from horses with hyperkalemic periodic paralysis. Ouabain, a cardiac glycoside, binds to the Na(+)-K(+)-adenosine triphosphatase (Na+ pump) and prevents active transport of Na+ and K+ across cell membranes. We used [3H]ouabain to quantify the number and affinity of Na+ pumps in skeletal muscle from Quarter Horses with the muscular disorder hyperkalemic periodic paralysis (HYPP). [3H]Ouabain-binding properties of gluteal muscle from clinically normal and affected horses were used to determine whether altered Na+ pump number or affinity could contribute to the pathologic features of muscle in affected horses. Foals and adult horses with HYPP we...
Clinical syndrome and diagnosis of hyperkalaemic periodic paralysis in quarter horses. Of the 16 horses studied, 14 belonged to a family previously shown to be susceptible to hyperkalaemic periodic paralysis (HPP), and 8 were shown to have HPP. Diagnosis of HPP by electromyographic detection of myotonic discharges or by oral administration of KCl to induce clinical signs and hyperkalaemia had similar reliability and gave the same result in 80% of cases. KCl had to be administered at doses up to 0.2 g/kg bodyweight to produce signs in some horses. KCl challenge testing was more time consuming than EMG and resulted in one fatality. Overall, electromyography and potassium challenge...
Genetic study of hyperkalemic periodic paralysis in horses. Four Quarter Horses (1 stallion, 3 mares) with hyperkalemic periodic paralysis were mated to unaffected horses to determine the genetic basis of the disease. The affected stallion was bred to 11 unaffected mares (4 Quarter Horses, 1 Arabian, 2 Standardbreds, and 4 Thoroughbreds). The 3 affected mares were bred to an unaffected Quarter Horse stallion. Of the 15 offspring obtained from these matings, 9 were affected with hyperkalemic periodic paralysis, and 6 were unaffected, consistent with an autosomal dominant mode of inheritance. Diagnosis was established by results of oral administration of...
Postanesthetic recumbency associated with hyperkalemic periodic paralysis in a quarter horse. Anesthesia and surgery in a Quarter Horse affected with hyperkalemic periodic paralysis resulted in euthanasia after 7 days of postoperative recumbency. Initial recovery was uneventful after extensive sinus surgery, but within 2 hours, the horse had severe muscle weakness. Plasma electrolyte concentrations were within the normal range during the period of recumbency. There was no clinical or laboratory evidence of severe muscle damage. Despite treatment with acetazolamide, isoproterenol, and intensive nursing, the horse was unable to stand for more than a few seconds and developed severe decub...
Periodic paralysis in quarter horses: a sodium channel mutation disseminated by selective breeding. We recently reported on a linkage study within a Quarter Horse lineage segregating hyperkalaemic periodic paralysis (HYPP), an autosomal dominant condition showing potassium-induced attacks of skeletal muscle paralysis. HYPP co-segregated with the equine adult skeletal muscle sodium channel alpha subunit gene, the same gene that causes human HYPP. We now describe the Phe to Leu mutation in transmembrane domain IVS3 which courses the horse disease. This represents the first application of molecular genetics to an important horse disease, and the data will provide an opportunity for control or e...
Effects of phenytoin in two myotonic horses with hyperkalemic periodic paralysis. The effects of phenytoin treatment were evaluated in 2 myotonic horses with hyperkalemic periodic paralysis (HPP). Phenytoin treatment abolished the clinical signs of muscle fasciculations following oral potassium challenge and decreased or abolished repetitive firing and myotonic discharges found on electromyographic examination. In both horses, an abnormally low threshold for calcium-induced calcium release was measured in heavy sarcoplasmic reticulum fractions from skeletal muscle, and this threshold increased with phenytoin treatment. Results suggest phenytoin is useful in modifying disord...
Respiratory stridor associated with polymyopathy suspected to be hyperkalemic periodic paralysis in four quarter horse foals. Four Quarter Horse foals ranging in age from 6 days to 2 months were determined to have upper airway stridor secondary to polymyopathy suspected to be hyperkalemic periodic paralysis. Electromyography revealed spontaneous muscle activity in all muscles examined. Electromyographic findings were similar in the dams of 3 foals (No. 1, 3 and 4). Hyperkalemia was found in foals 1 and 4. Endoscopically, the upper airway stridor in foals 1 and 3 was confirmed to be attributable to laryngeal and pharyngeal collapse or spasm. Foals 1, 2, and 3 were treated with acetazolamide. Foal 4 was not treated, at...
Familial incidence of hyperkalemic periodic paralysis in quarter horses. The pedigrees of 17 horses with hyperkalemic paralysis were studied. All were first-, second-, or third-generation offspring of a common sire, 16 were registered Quarter Horses. Analysis indicated that it was unlikely that the concentration of hyperkalemic periodic paralysis in the offspring of this sire was attributable to chance. The familial nature of this condition should help veterinarians diagnostically. It also suggests that it is possible to reduce the incidence of this condition by breeding from non-affected lines of horses and reinforces the need for studies to determine whether the ...
Inheritance of myotonic discharges in American quarter horses and the relationship to hyperkalemic periodic paralysis. Electromyography (EMG) was used to detect myotonic discharges in Quarter Horse breeding stock and to follow the results of mating horses with hyperkalemic periodic paralysis (HPP). The studies were performed on two brood mare farms. A total of six breeding stock showed myotonic discharges and 15 were nonmyotonic. Myotonic discharges were seen in five of six horses belonging to the blood line previously implicated as being predisposed to HPP. Two of these horses had shown clinical signs of HPP. Only one of 15 breeding horses unrelated to the HPP predisposed blood line showed myotonic discharges...
Linkage of hyperkalaemic periodic paralysis in quarter horses to the horse adult skeletal muscle sodium channel gene. A genetic disease observed in certain Quarter horses is hyperkalaemic periodic paralysis (HYPP). This disease causes attacks of paralysis which can be induced by ingestion of potassium. Recent studies have shown that HYPP in humans is due to single base changes within the adult skeletal muscle sodium channel gene. A large Quarter horse pedigree segregating dominant HYPP was studied to determine if mutations of the sodium channel gene are similarly responsible for HYPP in horses. We used cross-species, PCR-mediated, cDNA cloning and sequencing of the horse adult skeletal muscle sodium channel a...
Altered ionic permeability in skeletal muscle from horses with hyperkalemic periodic paralysis. A recently described disorder in certain registered Quarter horses bears many clinical similarities to the muscle disease identified as hyperkalemic periodic paralysis (HPP) in humans. Pathological changes in membrane permeability or Na(+)-K+ pump activity have been proposed to produce the muscle depolarization and inexcitability that characterize the condition in humans. Biopsies of external intercostal muscle from normal and affected horses were used to determine whether alterations in either permeability and/or pump activity could be linked to the pathology in horses. Affected horse muscle ...
Hyperkalemic periodic paralysis in horses. Eleven horses (3 mares, 7 stallions, 1 gelding) with clinical and biochemical evidence of hyperkalemic periodic paralysis were studied. Each horse had history of episodic weakness, muscular tremors, or collapse, which lasted for periods of a few minutes to hours. Diagnosis was based on hyperkalemia in association with a spontaneous episode of paralysis or by precipitation of an episode by oral administration of potassium chloride. Clinical and biochemical events were documented during spontaneous and induced episodes of muscular weakness. During episodes, electrocardiographic findings were con...
Use of electromyography for the diagnosis of equine hyperkalemic periodic paresis. The use of electromyography (EMG) as a diagnostic aid for equine hyperkalemic periodic paresis (EHPP) was investigated in seven affected and seven control horses. Affected horses were confirmed positive for EHPP either by elevated serum potassium concentration with clinical signs of myotonia, or by inducing hyperkalemia and clinical signs using oral potassium chloride challenge. All horses were asymptomatic at the time EMG was performed, using bipolar fine wire needle electrodes. The myopotentials were recorded on magnetic tape and displayed on paper charts for analysis. Insertional and restin...
Episodic muscle tremors in a quarter horse: resemblance to hyperkalemic periodic paralysis. A three year old Quarter Horse stallion was presented with a one year history of episodes of generalized muscle tremors and stiffness, and spasm of the muscles of facial expression, lasting 10-15 minutes. Between attacks, the horse was either normal or had a localized muscle tremor in the flank region. Episodes appeared unrelated to exercise. The major abnormal findings included 1) a rise in plasma potassium from a resting level of 4.4 to 7.9 mmol/L during an attack and 2) electromyographic findings of generalized increased insertion activity and myotonic discharges. The horse was treated with...
Relationship between potassium administration, hyperkalaemia and the electrocardiogram: an experimental study. Hyperkalaemia affected the equine myocardium. The minimum plasma potassium concentration required to induce electrocardiographic changes was 6.2 mmol/litre and severe cardiotoxic effects were observed at levels of 8.0 to 10.1 mmol/litre in this experimental situation. The most consistent sign of hyperkalaemia was broadening and flattening of the P wave, which was generally associated with a change in T waves in the chest lead from negative to positive. The more pronounced the hyperkalaemia, the less pronounced the P wave and the more peaked positive the T wave. Severe hyperkalaemia was associa...