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Quarter Horse
Hyperkalemic periodic paralysis
Related terms: HYPP
Outline: Hyperkalemic periodic paralysis is a muscle disorder that causes episodes of paralysis or muscle weakness. Horses with hyperkalemic periodic paralysis suffer with episodes of muscle spasms, weakness or paralysis. During these episodes, horses often experience respiratory distress due to paralysis of upper respiratory muscles. Environmental factors may increase the likelihood of a paralysis episode, including exposure to cold, stress, high-potassium diets, fasting, anaesthesia or heavy sedation.
Clinical signs of hyperkalemic periodic paralysis are most frequently observed in young horses, of 2-3 years of age. Episodes are relatively brief, and usually last for between 15 to 60 minutes each. This may mean they are missed by owners, especially when horses are kept at pasture.
Hyperkalemic periodic paralysis has been associated with descendants of a popular Quarter horse sire called Impressive, and may occur in approximately 1 in 20 of all Quarter horses.
Summary of Information
(for more information click on the links below)
1. Brief description
Hyperkalemic periodic paralysis is a muscle disorder that causes episodes of paralysis or muscle weakness. It is caused by a genetic defect affecting muscles cells, specifically their ability to transport sodium ions across their cell membranes. This interferes with their ability to contract normally in response to electrical nerve signals resulting in involuntary muscle contraction (spasms) and muscle weakness. Affected animals experience spontaneous episodes of muscle tremors, weakness, paralysis and collapse, often accompanied by respiratory distress.
2. Intensity of welfare impact
Horses with hyperkalemic periodic paralysis suffer from episodes of muscle spasms, weakness or paralysis. During episodes, horses often experience breathlessness and respiratory distress due to paralysis of upper respiratory muscles.
Horses with two copies of the mutated gene (ie homozygous for the mutated gene) are affected more severely, with more frequent episodes of weakness or paralysis and more severe signs of upper airway obstruction. Horses may die suddenly during severe episodes due to asphyxiation (due to respiratory muscle paralysis) or heart failure. Respiratory distress may result in apprehension or fear. Emergency treatment may be required during attacks, and in severe cases of respiratory distress, horses may require a tracheotomy.
Environmental factors that may increase the likelihood of a paralysis episode include exposure to cold, stress, high-potassium diets, fasting, anaesthesia or heavy sedation.
3. Duration of welfare impact
Clinical signs of hyperkalemic periodic paralysis are most frequently first observed in young horses, of 2-3 years of age. Affected horses will experience paralytic episodes throughout their life.
Episodes are usually brief, and usually last for between 15 to 60 minutes each. This may mean that they are missed by owners, especially when horses are kept at pasture.
4. Number of animals affected
In a study of 978 Quarter horses between 1989 and 1991, it was found that 43 horses (4.4%) had the gene mutation responsible for hyperkalemic periodic paralysis and all affected horses were traced back to a single ancestral sire called Impressive.
Hyperkalemic periodic paralysis affects males and females equally frequently.
5. Diagnosis
The most sensitive test for hyperkalemic periodic paralysis is the gene probe for hyperkalemic periodic paralysis–type sodium channel mutation (ie DNA testing). Diagnosis can also be made based on the clinical signs, together with elevated blood potassium levels, although potassium levels in the blood may not always be outwith the normal range expected.
6. Genetic
Hyperkalemic periodic paralysis has been associated with a popular Quarter horse sire called ‘Impressive’.
Hyperkalemic periodic paralysis is inherited as an autosomal dominant trait, which means it can occur in both males and females and only one copy of the gene is required to produce the disease. If two heterozygous affected horses (carrying only one copy of the mutated gene) are bred together, approximately 50% of the offspring will be heterozygous and affected, 25% will be homozygous and affected (ie will carry two copies of the mutated gene) and 25% will be normal (ie will not carry the mutation). Breeding a heterozygous affected horse with a normal horse will result in approximately 50% normal offspring and approximately 50% heterozygous affected offspring.
7. How do you know if an animal is a carrier or likely to become affected?
A genetic test is available for the detection of the genetic defect causing hyperkalemic periodic paralysis in horses. It can detect homozygous (two copies of the mutation) and heterozygous (one copy of the mutation) affected horses, as well as non-affected (no gene mutation) horses.
8. Methods and prospects for elimination of the problem
The specific mutation is known to exist in descendants of the stallion ‘Impressive’, and all descendants should be tested before breeding.
Mandatory testing for hyperkalemic periodic paralysis was introduced by the American Quarter Horse Association in 1996, and homozygous affected horses are not eligible for breeding. Breeding from two heterozygous affected horses will also produce affected offspring, and so this should also be avoided, where possible.
For further details about this condition, please click on the following:
(these link to items down this page)
- Clinical and pathological effects
- Intensity of welfare impact
- Duration of welfare impact
- Number of animals affected
- Diagnosis
- Genetics
- How do you know if an animal is a carrier or likely to become affected?
- Methods and prospects for elimination of the problem
- Acknowledgements
- References
1. Clinical and pathological effects
Hyperkalemic periodic paralysis is a muscle disorder that results in episodes of paralysis or muscle weakness. It is caused by a genetic defect that affects muscles cells, specifically their ability to transport sodium ions across their cell membranes, and this interferes with their ability to contract normally in response to electrical nerve signals to do so.
The neuromuscular system is comprised of peripheral nerves, muscles and the junctions between muscle and the nerve – the synapse - and is the means by which the contraction of the muscles is controlled. Cells in the motor neuron, which innervate muscle fibres, communicate electrical signals to each other via action potentials, short-lasting events in which the electrical potential of the cell membrane rises and falls. Action potentials are generated by voltage-gated ion channels in the plasma membrane of the cell. Formed from pore-forming membrane proteins, these ion channels control the flow of ions across the cell membrane and open or close in response to electrical signals. Ion channel gates only allow charged ions of a certain size and/or charge to pass through (selective permeability). These channels are shut when the electrical membrane potential of a cell is at rest ie its resting potential. At rest, cell interiors have a negative charge compared to the exterior of the cell. Once the membrane potential increases to a threshold value, it allows an inward flow of positively charged sodium ions via sodium ion channels (depolarisation) in to the cell. The influx of sodium alters the electrochemical gradient between the inside of the cell and the outside, and more channels open, producing a greater electrical current across the cell membrane. This process continues until all of the sodium channels are open, producing a large spike in the membrane potential and an action potential. Following depolarisation, the rapid influx of sodium ions causes the polarity of the plasma membrane to reverse, so that the inside of the cell membrane is now positive compared to the outside, and the sodium ion channels become inactivated and potassium ion channels are activated. Positively charged potassium ions now leave the cell which, in turn, brings the charge inside the cell back to its resting state (repolarisation). These changes in turn trigger the release of calcium ions causing the muscle to contract.
In animals with hyperkalemic periodic paralysis, there is a genetic mutation resulting in a change to the shape of the sodium channel membrane proteins and this interferes with their normal function (Bowling et al 1996). The sodium channels become leaky, and the cell membrane more permeable to sodium, which alters the balance of sodium and potassium across the cell membrane, and thus results in reduced depolarisation. Of the two ions, muscle cells are more sensitive to changes in the level of potassium ions. Whilst the level of potassium in the blood may not rise above normal values, horses with this mutation are more sensitive to increased levels of potassium. Sodium channels open normally in the initial phase of the action potential, but the faulty sodium channels then fail to inactivate and close properly, leading to excessive influx of sodium ions into the cell. This causes prolonged individual action potentials and thus a prolonged signal for the cells to contract leading to involuntary muscle contraction (spasms). The excess of sodium ions also prevents the nerve from repolarising, so that it can generate the next action potential, causing muscle weakness because the muscle cannot react and contract when it receive the signal to do so (Pickar et al 1991; Spier et al 1990). Affected animals experience spontaneous episodes of muscle tremors, weakness, paralysis and collapse. These episodes are often accompanied by respiratory distress, due to muscle weakness of the upper respiratory airways.
2. Intensity of welfare impact
Horses with hyperkalemic periodic paralysis suffer with episodes of muscle spasms, weakness or paralysis (Naylor 1994a). During mild episodes, horses remain standing but in more severe episodes, horses may sway, stagger, sit (like a dog would) or lie down. During episodes, horses often experience breathlessness and respiratory distress due to paralysis of upper respiratory muscles, which may cause apprehension and fear.
Horses with two copies of the genetic mutation (ie homozygous for the mutated gene) are affected more severely, with more frequent episodes of weakness or paralysis and more severe signs of upper airway obstruction (Naylor 1994b). Horses may die suddenly during severe episodes due to asphyxiation (due to respiratory muscle paralysis) or heart failure. Emergency treatment may be required during attacks, and in severe cases of respiratory distress, horses may require a tracheotomy.
Environmental factors may increase the likelihood of paralysis episode, including exposure to cold, stress, high-potassium diets, fasting, anaesthesia or heavy sedation (Reynolds et al 1998; Spier 2006). Affected horses can be placed on long-term management programmes, such as low-potassium diets (eg whole grains) or medicines to get rid of excessive potassium, to try to alleviate the effects of the mutation.
3. Duration of welfare impact
Clinical signs of hyperkalemic periodic paralysis are most frequently observed in young horses, of 2-3 years of age (Cox & DeBowes 1990) although affected horses experience paralytic episodes throughout their life.
Heterozygous affected horses may develop clinical signs after weaning (ie after 6 months) and generally show intermittent episodes of weakness or paralysis with no apparent abnormalities between episodes. Homozygous affected horses may show clinical signs from an earlier age, and experience more frequent and more severe clinical episodes and effects
Episodes are generally brief, and usually last for between 15 to 60 minutes each. This may mean they are missed by owners, especially when horses are kept at pasture.
4. Number of animals affected
In a study of 978 Quarter horses between 1989 and 1991, it was found that 43 horses (4.4%) had the gene mutation responsible for hyperkalemic periodic paralysis and all affected horses were traced back to a single ancestral sire called ‘Impressive’ (Bowling et al 1996).
Hyperkalemic periodic paralysis can affect males and females equally, although the clinical signs are reported more often for males; this may be because it is more noticeable in males raised for showing as they are under closer observation (Naylor 1994a).
5. Diagnosis
The most sensitive test for hyperkalemic periodic paralysis is the gene probe for hyperkalemic periodic paralysis–type sodium channel mutation (ie DNA testing). Diagnosis can also be made based on the clinical signs, together with elevated blood potassium levels, although potassium levels in the blood may not be outwith the normal range. Otherwise, hyperkalemic periodic paralysis can be misdiagnosed as colic, rhabdomyolysis (‘tying up’ or muscle breakdown) and accidental recumbency during transportation (Naylor 1994a).
6. Genetics
Hyperkalemic periodic paralysis has been associated with descendants of a popular Quarter horse sire called ‘Impressive’ (Bowling et al, 1996). Horses from this sire, some of which are likely to have inherited the gene that causes hyperkalemic periodic paralysis, may have been preferentially selected as breeding stock because they had favourable well-developed musculature and had good results in halter horse shows (Naylor 1994b).
Hyperkalemic periodic paralysis is inherited as an autosomal dominant trait, which means it can occur in both males and females and only one copy of the gene is required to produce the disease. If two heterozygous affected horses (carrying only one copy of the mutated gene) are bred together, approximately 50% of the offspring will be heterozygous and affected, 25% will be homozygous and affected (ie will carry two copies of the mutated gene and 25% will be normal (ie will not carry the mutation). Breeding a heterozygous affected horse with a normal horse will result in approximately 50% normal offspring and approximately 50% heterozygous affected offspring.
7. How do you know if an animal is a carrier or likely to become affected?
A genetic test is available for the detection of the genetic defect causing hyperkalemic periodic paralysis in horses. The test is usually conducted with blood samples, but can be done non-invasively, using hairs with roots. It can detect homozygous (ie two copies of the mutation) and heterozygous (ie one copy of the mutation) affected horses, as well as non-affected (no gene mutation) horses.
The genetic mutation has been linked to a single common ancestor, and so descendants of this horse (Impressive) are more likely to carry the mutation and therefore be affected.
8. Methods and prospects for elimination of the problem
Mandatory testing for hyperkalemic periodic paralysis was introduced by the American Quarter Horse Association in 1996, and homozygous affected horses are not eligible for breeding.
Breeding from heterozygous affected horses will also produce affected offspring, and so this should also be avoided, where possible.
The specific mutation is known to exist in descendants of ‘Impressive’, and all descendants of this horse should be tested before breeding. Descendants of this bloodline have also been used in other breeds, such as Paint horses and Appaloosas (Cox & DeBowes 1990).
It is not currently known whether different genetic mutations causing hyperkalemic periodic paralysis are present in other bloodlines.
9. Acknowledgements
UFAW thanks Dr Emma Buckland (BSc PhD), Dr David Brodbelt (MA VetMB PhD DVA DipECVAA MRCVS) and Dr Dan O’Neill (MVB BSc MSc PhD MRCVS) for their work in compiling this section.
10. References
Bowling AT, Byrns G and Spier S (1996) Evidence for a single pedigree source of the hyperkalemic periodic paralysis susceptibility gene in quarter horses. Animal Genetics 27: 279–81
Cox JH and DeBowes RM (1990) Episodic weakness caused by hyperkalemic periodic paralysis in horses. Compendium on Continuing Education for the Practicing Veterinarian 12, 83–86. doi:ISSN: 0193-1903
Naylor JM (1994a) Equine hyperkalemic periodic paralysis: review and implications. The Canadian Veterinary Journal 35: 279–85
Naylor JM (1994b) Selection of quarter horses affected with hyperkalemic periodic paralysis by show judges. Journal of the American Veterinary Medical Association 204: 926–8
Pickar JG, Spier SJ, Snyder JR and Carlsen RC (1991) Altered ionic permeability in skeletal muscle from horses with hyperkalemic periodic paralysis. The American Journal of Physiology 260: C926–33
Reynolds JA, Potter GD, Greene LW, Wu G, Carter GK, Martin MT, Peterson TV, Murray-Gerzik M, Moss G and Erkert RS (1998) Genetic-diet interactions in the hyperkalemic periodic paralysis syndrome in quarter horses fed varying amounts of potassium: III. The relationship between plasma potassium concentration and HYPP Symptoms. Journal of Equine Veterinary Science 18: 731–735. doi:10.1016/S0737-0806(98)80503-0
Spier SJ (2006). Hyperkalemic periodic paralysis: 14 years later. In: Proceedings of the 52nd Annual American Association of Equine Practitioners Convention. San Antonio, TX, pp. 1–5
Spier SJ, Carlson GP, Holliday TA, Cardinet GH and Pickar JG (1990) Hyperkalemic periodic paralysis in horses. Journal of the American Veterinary Medical Association 197: 1009–17
© UFAW 2016
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