On a day like any other, at the 1970 Indiana State Fair, a beautiful yearling Quarter Horse colt was sold, with no idea of the legacy he would one day hold. His name was Impressive. His prominent muscular build and show record would be nothing short of impressive, producing a blue ribbon literally every time he stepped in the ring (Moore et al. 1993). Naturally, breeders would flock to this stallion, eager to have his bloodlines in their stock. His progeny would even stretch into the Paint, Appaloosa, and even Arab breeds (Press Release, 2003; Spier, 2007). Little did anyone know that his DNA carried one important mutation that would deliver a disastrous blow to the Quarter Horse industry (Spier, 2007). This one little colt would introduce hyperkalemic periodic paralysis to thousands of horses around the world (Moore et al. 1993; Sellnow, 2001).
HYPP, also known as Impressive Syndrome, is a genetically inherited disease which causes unpredictable involuntary and uncontrollable muscle action, the symptoms of which can only be controlled by diet and can never be completely cured (Adams, date unknown; Evers, 2004; Moore et al. 1993; Loving, 2007; Sellnow, 2001; Spier, 2007). In very severe cases, HYPP can be dangerous and potentially fatal. Affected horses may need to be medicated for their entire lives, but others can see success with only a strict diet and sufficient supplementation and water consumption. For affected horses, the contents of the forage they are eating and the overall level of potassium in their diet can mean the difference between life and death. It is therefore imperative that the owners of these animals be aware of the unique nutritional needs resulting from this syndrome.
It can be difficult to pinpoint HYPP as the cause for its many physical symptoms, and it is possible for afflicted horses to show no symptoms at all. The lack of symptoms, however, does not mean that the condition is not present. The only way to definitively diagnose a horse with HYPP is a genetic test done on mane or tail hairs (Adams, date unknown; Press Release 2003; Sellnow, 2001; Spier, 2007). There are many physical indications, however, that can be warning signs for the owners of Quarter Horses, Paints, and Appaloosas, several of which can cause a misdiagnosis as a more common problem in the absence of the genetic test.
Every horse is different, and different horses will experience varying degrees of severity in their physical symptoms. Horses that contain two copies of the mutated gene, homozygous, will usually experience the worst attacks, but horses that have only one copy of the defective gene, heterozygous, may only experience mild symptoms. A horse will normally exhibit some symptoms by the age of two or three if they suffer from the disease, but it is possible for a horse to go much longer, or even their entire lives, without an attack or any physical indication at all (Moore et al. 1993; Loving, 2007; Spier, 2007). For most horses, however, this is a rarity. Outside of the hyperkalemic episodes, affected horses will generally demonstrate frequent urination and possibly excessive elimination of solid waste as well as a method of excreting surplus potassium from the blood serum. They may also appear antsy or anxious, or conversely they may seem depressed or bored (Steward, date unknown). Aside from this, horses generally appear normal in between attacks.
Episodes of HYPP are not necessarily as easy to distinguish as one might think. For horses experiencing a mild episode, they may simply twitch slightly, as if trying to rid themselves of a pesky fly, and they might begin to sweat (Steward, date unknown). They may also exhibit a stiff gait and hardened muscles, which leads many to believe that their horses are ‘tying up’ (Moore et al. 1993; Steward, date unknown). The important difference to note is how the horse behaves over time. Horses that have tied up tend to remain stiff for an extended period of time, where as a horse which has undergone an attack of HYPP will be fine once the episode is over (Moore et al. 1993; Spier, 2007). Incidences of HYPP may also be triggered by stimuli other than exercise, where tying up is usually solely the result of physical activity.
More intense attacks can also be confused with other medical ailments or conditions. Muscle weakness is very common with the muscle spasms, and can be so extreme that the horse will sway and stagger, and eventually its legs may give out, causing it to sit or lay down (Steward, date unknown). Once the horse is down, it will likely be unable to get back up, or at least experience sufficient difficulty in doing so for the length of the episode. Many owners will witness this and misdiagnose the horse with colic because of the apparent reluctance to stand up. In very severe attacks, the affected horse may even seem to be suffering from a seizure, but unlike a seizure, horses are fully conscious and aware of their environment during an episode of HYPP (Moore et al. 1993). The third eyelid may also be seen distending during certain attacks (Adams, date unknown; Spier, 2007; Steward, date unknown).
Unfortunately, the spells can produce even worse symptoms than these. In the most heartbreaking of incidences, horses can experience difficulty breathing from the paralysis of tracheal and other respiratory muscles. If this persists for too long without an emergency tracheotomy, the horse can die from respiratory failure (Sellnow, 2001; Spier, 2007; Steward, date unknown). Horses can also collapse suddenly and pass away from cardiac arrest (Steward, date unknown). While this is not particularly common, it is a tragic testament to the true danger of HYPP.
Given the complexity of genetic material and cell functions, it can be hard to believe that one little amino acid could have such a profound effect on a horse. The mutated gene associated with HYPP causes what is called a substitution point mutation in the coding for the alpha subunit protein of the sodium ion channel (Spier, 2007). When the cell is building the protein, the messenger RNA tells the transfer RNA to place the amino acid leucine where phenylalanine should be in the sequence. Point mutations are often silent, which means that they produce no noticeable effect, but unfortunately HYPP affects one of the key parts of the skeletal muscular system, resulting in the failure of a negative feedback loop to inhibit muscular activity.
The sodium-potassium pump (see Appendix A) is a protein mechanism in the cell membranes of nerve cells: one unit allows positively charged potassium ions to enter the cell, while the other unit facilitates the movement of positively charged sodium ions out of the cell. For every two potassium ions that enter the cell, three sodium ions exit. This causes a buildup of positive charges to accumulate outside of the cell, which is called an electrochemical potential gradient. This difference in charge is what allows nerve cells to fire the action potentials, or electrical impulses, which result in muscular movement. When the level of potassium in the blood serum rises, the sodium channels are supposed to close. Because this does not happen in horses with HYPP, the sodium ions rush into the cell where sodium concentrations are low, potassium leaks into the bloodstream, and the membrane loses its polarized charge, resulting in paralysis (Moore et al. 1993; Loving, 2007; Sellnow, 2001; Spier, 2007).
While it is well known what is biologically responsible for the disease as a whole, it is much more difficult to pinpoint what triggers an attack. Periods of stress generally increase the frequency and likelihood of episodes, but the type of stress can vary. Anesthesia is a major stimulus of HYPP attacks that should be avoided if at all possible. If it is absolutely necessary, a vet must be warned of the horse’s disease before the anesthesia is administered to prepare the horse, possibly by administering treatment, and to prepare emergency treatment (Adams, date unknown; Evers, 2004; Moore et al. 1993; Loving, 2007; Sellnow, 2001; Spier, 2007). Similarly, heavy sedation is also known to be associated with spells. Exercise itself has not been conclusively tied to the onset of symptoms, but horses can tend to experience attacks during the rest period after exercise (Sellnow, 2001). While horses generally do not experience any symptoms during exercise, anyone unfamiliar with the disease, symptoms, and treatment should refrain from riding affected horses just in case (Sellnow, 2001). Trailering is also a common stressor that can increase the chance of a spell (Moore et al. 1993). The presence of a second disease may make the horse prone to episodes, as might the stress put on the body by pregnancy and exposure to extreme cold (Moore et al. 1993; Spier, 2007).
Most commonly, however, the physical symptoms of HYPP are associated with fluctuations in a horse’s diet. Ingesting high, or even seemingly normal, amounts of potassium is a very common predecessor of attacks. Even with low potassium diets, horses are generally more prone to attacks after eating (Adams, date unknown). Any dietary changes in either the feed itself or the feeding schedule can also trigger episodes. Many horses are able to adjust their eating habits over a period of weeks, but spells are still possible, even if it is done gradually and carefully. Fasting also places stress on the horse and makes it prone to attacks (Spier, 2007). Though there is not enough research at this time to conclusively detect what exactly happens in the horse that prompts an attack, there is so much known about HYPP already compared to many other disorders that there is not as much focus on HYPP research at this point, though muscular disorders in general are still a subject of significant scientific interest (Brewer, date unknown). With strategies for controlling the symptoms and a definitive method of prevention, however, it is possible to care for horses currently suffering and completely eradicate the disease in the future even without this information.
Because HYPP is a genetic defect, there is no cure, but there are many adjustments that can be made to make living with the disease easier. The primary treatment option that the vast majority of horses find effective in reducing the frequency of episodes is a diet low in potassium with ample salt and water for consumption (Adams, date unknown; Evers, 2004; Moore et al. 1993; Loving, 2007; Sellnow, 2001; Spier, 2007). Potassium in HYPP horses should be kept between 0.6% and 1.1% by weight of the horse’s total diet, with no one meal containing more than 33 grams of potassium (Evers, 2004). Decreasing the amount of potassium in the bloodstream decreases the concentration gradient along which the ions travel when the channel fails to close and protects the electrochemical potential for electrical impulse. The only way for the horse to eliminate excess potassium is by excreting waste, which is where the water and salt are beneficial (Evers, 2004). Increased water ingestion understandably raises urine production, and higher salt concentrations in the blood encourage the nephron to reabsorb more water to send to the kidneys, thereby also increasing urine production. These horses should also be fed small meals throughout the entire day to avoid sudden fluctuations in blood potassium levels. Grass hay is preferred over alfalfa hay, but alfalfa mixed with grass or oat hay and oats for grain can also be an acceptable diet (Sellnow, 2001; Spier, 2007). Beet pulp is also an excellent feed for HYPP horses and provides them with both fiber and calories (Spier, 2007; Steward, date unknown). If the ratio of potassium and calcium become a concern, the horses can be supplemented with calcium carbonate, which can also promote potassium excretion in waste from the kidneys (Harrison, date unknown). If the horse can live off of pasture alone, that is the best option, but regardless of their diet, affected horses benefit with maximum turnout and a regular feeding schedule (Moore et al. 1993; Sellnow, 2001).
If diet is not enough to manage a horse’s attacks, there are also medications to help inhibit them and treat mild episodes when they occur. Many competition horses with HYPP are given acetazolamide with a diuretic, but the drug is considered an illegal substance under show rules and should be used with caution. Some horses will remain on the drug for the duration of their lives. Acetazolomide can also be given orally to treat a mild attack once warning signs appear. It increases the potassium excretion by the kidneys and influences glucose metabolism, which increases potassium uptake in cells. It is also an important therapy to be used before and after anesthesia or surgery to try and prevent paralysis (Adams, date unknown; Evers, 2004; Sellnow, 2001). Feeding a small amount of Karo syrup has been known to be very effective in reducing symptoms and avoiding a worse episode (Adams, date unknown; Steward, date unknown). If Karo syrup is unavailable, grain will have the same effect; the carbohydrates become glucose, which causes the release of insulin (Spier, 2007). The insulin then encourages the cells to take in more potassium. Light exercise, only by walking or lunging, can also relieve physical symptoms through the production of epinephrine, which can replace potassium in cells. This must be done with extreme caution, however, since the horse can possibly fall. In extreme cases, a diluted solution of calcium gluconate can also provide rapid relief (Spier, 2007).
HYPP is a disease that is completely incurable and possible to treat, yet it is entirely preventable. As of this year, all Quarter Horse foals which have the defective gene must be registered as carriers, and homozygous carriers will be unable to register (Press Release, 2003). It is altogether possible to completely eradicate the disease by simply refusing to breed carriers. Even heterozygous individuals pose the potential thread of passing on the disease (see Appendix A), but by simply refraining from breeding these horses, all of the treatments and management techniques could go unused and no horses would have to suffer the unintentional wrath of Impressive’s DNA. Yet despite this seemingly simple solution, the number of afflicted horses has actually experienced a gradual increase over time (Brewer, date unknown; Loving, 2007). Though carriers tend to have the same award-winning build as their famous ancestor, there is no correlation between the gene and muscle formation (Brewer, date unknown). There is no genetic reason for breeders to spread this mutation with the potential to take lives. Nutritional management should not be abused as an excuse to breed these horses, but rather a fortuitous therapy for those who were put in this situation before the choice became clear. Diet may successfully treat the symptoms of HYPP, but breeders are the only true cure.
The Seven Point Reference Guide for HYPP
• Before breeding or purchasing a Quarter Horse, Appaloosa, Paint, or any other horse you know to have Quarter Horse bloodlines, check the horse’s pedigree to see if it dates back to AQHA #0767246 Impressive. If it does, send a sample of mane or tail hairs to a lab for HYPP testing. This is the only way to diagnose and prevent a life with HYPP.
• A horse that tests positive for one copy of the mutated gene will still suffer from the disease and have a fifty percent chance of passing it on to offspring. While heterozygous horses may not exhibit symptoms or experience attacks as severe as horses with two copies of the gene, they are still afflicted and need careful maintenance.
• All affected horses should be placed on a low potassium diet and constantly have access to fresh water and plain white salt to help flush out excess potassium. A horse’s total potassium intake should be no higher than 0.6% to 1.1% by weight and no one meal should contain more than 33 grams. Decreased potassium should lower the frequency of episodes.
• If diet is not enough to sufficiently manage HYPP in a particular horse, acetazolamide is a drug known to reduce episodes and successfully treat mild attacks.
• Avoid stressful situations such as shipping, anesthesia, surgery, and pregnancy if at all possible. Horses often experience more spells under these circumstances.
• For mild attacks, introducing carbohydrates via Karo syrup or grain can help prevent the spell from worsening. Light exercise can also be beneficial, but must be done extremely carefully in case the horse falls from muscle weakness.
• If a horse is having an attack and is already lying down, do not get the horse up. For all serious spells, a veterinarian should be called immediately as respiratory arrest may occur.