By Dr. Sharon Spier and The American Association of Equine Practitioners
What’s The Hype Over HYPP?
Questions answered regarding hyperkalemic periodic paralysis
“HYPP” has been the buzzword around certain show circuit circles since 1992. It has made some horsemen turn white, some others turn red and still others shrug their shoulders. What is the big deal about this disease?
The American Association of Equine Practitioners and Dr. Sharon Spier from the University of California at Davis have collaborated to respond to many unanswered questions about HYPP. Education about HYPP can reduce its spread and severity.
What is the cause?
Hyperkalemic periodic paralysis (HYPP) is an inherited disease of the muscle, which is caused by a genetic defect. A point mutation in DNA exists in the sodium channel gene, which codes for an abnormal channel to be expressed in skeletal muscle. This mutation is passed on to offspring.
Sodium channels are “pores” in the muscle cell membrane which control contraction of the muscle fibers. When the defective sodium channel gene is present, the channel becomes “leaky” and makes the muscle overly excitable and contract involuntarily. The channel become “leaky” when potassium levels fluctuate in the blood. This may occur with fasting followed by consumption of a high potassium feed such as alfalfa. Hyperkalemia, which is an excessive amount of potassium in the blood, causes the muscles in the horse to contract more readily than normal. This makes the horse susceptible to sporadic episodes of muscle tremors or paralysis.
This genetic defect has been identified in offspring of the American Quarter Horse sire, Impressive. To date, confirmed cases of HYPP have been restricted to descendants of this horse.
How is it spread?
HYPP is an autosomal dominant genetic trait, which means only one copy of the gene is required to produce the disease, and that the disease can equally occur in both sexes (mare, gelding and stallion).
To elucidate, suppose a mare has tested “HYPP H/N.” This means she is heterozygous, or carries one copy of the HYPP gene. Breeding her to a normal sire, or HYPP N/N, will result in a 50 percent chance the offspring will carry the HYPP gene (HYPP H/N) and a 50 percent chance of the foal being normal. Breeding her to a heterozygous sire, or HYPP H/N, will cause only a 25 percent chance of the offspring being normal (HYPP N/N), a 50 percent chance of the offspring to carry the gene (HYPP H/N) and 25 percent chance of the offspring to be homozygous (HYPP H/H, or carry both copies of the HYPP gene).
A carrier of the defect (HYPP H/N) is affected with HYPP. These horses can show clinical signs of the disease and can pass the gene on to their offspring. Though horses, which are homozygous affected (H/H), show more severe clinical symptoms, heterozygotes also have abnormal muscle function because it is a dominant trait.
Are there any signs?
Diagnosis of HYPP can be difficult based simply on observance of the horse. There are many different symptoms, which can mimic other diseases such as “tying-up” or colic. Classic signs include periodic attacks of muscle spasms, tremors, weakness, sweating and recumbency. During any attack, the horse may have rapid, labored or difficult breathing. Homozygotes will have noisy breathing due to paralysis of the muscles in the throat.
Furthermore, severity of clinical signs and frequency of episodes vary among horses even though they possess the same genetic defect. The duration of clinical signs also varies with episodes of muscle tremors or paralysis lasting only minutes to three hours or more.
“The classification of severity of clinical signs and frequency of episodes is difficult,” Dr. Sharon Spier states, “because horses may experience spasms that are not witnessed.”
In fact, some HYPP-affected horses may show no signs at all. Most horses appear clinically normal the majority of the time. This makes the disease even more difficult to detect.
So how can you tell if your horse has HYPP?
“In order to verify that a horse has HYPP,” Dr Spier states, “a DNA test on hair roots must be performed by a licensed laboratory such as the Veterinary Genetics Laboratory at the University of California, Davis.”
How common is HYPP?
Another study by Dr. Spier determined the frequency of the HYPP gene in the horse population. The study found that the gene is not being diluted in subsequent generations. Approximately 4 percent of Quarter Horses are affected, and unfortunately the frequency has not decreased since testing has become available.
In still another study to determine the gene frequency, 1,000 horses of different bloodlines were chosen at random by the University of California at Davis to test for HYPP. The data concluded that the HYPP gene is infrequent among Quarter Horses, yet is substantially linked to pedigrees tracing back to the popular sire Impressive.
What about testing?
All offspring of Impressive should be tested for HYPP. Horses with suspicious symptoms of the disease should also be tested.
Testing can be performed by contacting the Veterinary Genetics Laboratory at the University of California, Davis. (www.vgl.ucdavis.edu).
Can management induce or reduce an HYPP attack?
Environmental factors can actually cause an attack of muscle weakness. Owners of HYPP-positive horses should be aware that external stimulus and events could increase the chance of paralysis onset. These factors include dietary changes, fasting, general anesthesia, and concurrent illness and exercise restriction.
“Management factors remain an important cause of symptoms,” Dr. Spier states. “Owners of affected horses should be aware of the possible precipitating factors and be able to treat or manage the symptoms.
Dietary management is extremely important in the management of affected horses. Dietary adjustments include (1) avoiding high potassium feeds such as alfalfa hay, brome hay, soybean meal, and sugar molasses and beet molasses, and replacing them with timothy or Bermuda grass hay, grains such as oats, corn, wheat and barley, and beet pulp; (2) feeding several times a day; and (3) exercising regularly and/or being allowed frequent access to a large paddock or yard. Keeping the horse on pasture works well because due to the high water content of pasture grass, the horse is unlikely to consume large amounts of potassium in a short period of time. If the horse is experiencing problems on its present diet, it is recommended to feed a diet containing between 0.6 percent and 1.5 percent total potassium concentration. As there is a wide variation in potassium concentration of forages depending on maturity and soils, it is advisable to have feeds analyzed for potassium concentrations and other nutrient requirements. Complete feeds low in Potassium are commercially available. Alternatively, diets can be formulated such as the following, which will result in total K+ content of approximately one percent:
4.54 kg of late bloom timothy or similar low K+ grass hay
2.27 kg of shredded, soaked beet pulp (without molasses)
2.27 kg oats, divided into small frequent feedings.
Several drugs have been used for prevention of clinical episodes of paralysis. Horses have been treated with either acetazolamide (2 – 3 mg/kg orally, every 8 to 12 hours) or hydrochlorthiazide (0.5-1 mg/kg orally, every 12 hours) with apparent success. These agents exert their effects through different mechanisms; however, both cause increased renal potassium ATPase activity. Acetazolamide has been shown to stabilize blood glucose and potassium by stimulating insulin secretion.
Maintain a regular feeding and exercise schedule and avoid fasting or water deprivation. These horses do better if allowed access to a paddock or pasture rather than strict stall confinement. Daily or nightly turnout is also helpful. Avoid rapid changes in the diet.
Feeds that contain beet pulp (without molasses) have lower potassium than forages. For horses experiencing problems, an analysis of the feeding ration should be performed by your veterinarian or nutritionist for a selected diet lower in potassium (<1.5 percent). The dietary requirement for horses for potassium is 0.6 percent. Many grains are very low in potassium (0.5 percent), but molasses is very high in potassium (>3 percent) and should be avoided. Access to a salt or mineral block is also important.
Inform your veterinarian of the HYPP condition prior to any general anesthesia, as this may precipitate an episode of paralysis. If your horse is receiving medication, maintain him or her on therapy before and after surgery or anesthesia. Use common sense while hauling and be sure to stop and water horses frequently (every two hours).
“Many horses with this trait are asymptomatic and have very successful careers,” Dr. Spier comments. “Most horses can be easily managed with good care and can still bring great pleasure to their owners.”
Should an HYPP-positive horse be ridden?
According to Dr. Spier’s studies, the chance of a paralysis episode occurring while the horse is being ridden is unlikely. However, muscle spasms are unpredictable and can occur with only slight symptoms. Therefore, it is recommended that only experienced horsemen (those aware of symptoms and familiar with the horse’s behavior) handle and ride affected horses.Affected horses are not suitable for young riders.Contact a veterinarian immediately if any abnormal clinical signs are observed.
What if my horse goes into a mild HYPP episode?
Dr Spier recommends the following procedure for mild episodes of an HYPP attack (muscle tremors, but the horse is not down)
- Contact your veterinarian immediately.
- Exercise the horse (walking or longeing). Use caution as the horse could stumble and fall.
- Exercise stimulates adrenaline, which helps reduce potassium inside cells.
- Feed dry grain (oats, or corn-oats-barley, or you may use light Karo syrup for a glucose supplement). Feeding carbohydrates supplies glucose, which stimulates the release of insulin, which promotes potassium uptake in cells.
In SEVERE cases, a veterinarian may administer intravenous calcium gluconate (0.2 to 0.4 ml/kg of a 23 percent solution diluted in 1 liter of 5 percent dextrose), which usually provides immediate improvement. An increase in extra cellular calcium concentration raises the muscle membrane threshold potential, which decreases membrane hyperexcitability. To reduce the serum potassium, intravenous dextrose (6 ml/kg of a 5 percent solution) alone or combined with sodium bicarbonate (1 to 2 mEq/kg) can be used to enhance intracellular movement of potassium. With severe respiratory obstruction, a tracheotomy may be necessary. For severe cases with prolonged recumbency (>8 hours), which can lead to ischemic rhabdomyolysis, the use of slings has resulted in successful recovery.
What is the prognosis for HYPP-positive horses?
The prognosis for life for heterozygous affected horses (N/H) is good, although recurrent bouts of the disorder may occur. The feeding of diets low in potassium and maintenance therapy with diuretics may aid in making long-term maintenance more severely affected horses. Homozygous affected horses (H/H) have a poorer prognosis for normal life and can be difficult to manage.
Considering the autosomal-dominant transmission of this disorder, owners of affected horses should be strongly discouraged from breeding these animals for the long-term health of the Quarter Horse and other related breeds. Owners of affected horses should use caution when handling or riding affected horses and be aware of the clinical symptoms of this disease.
Biographical information: Dr. Sharon Spier is a Professor in the Department of Medicine and Epidemiology at the University of California at Davis. She is the Chief of Service in the Equine Field Service. Her clinical interests are in general equine practice, internal medicine disorders including diseases of muscle and gastrointestinal disorders. Dr. Spier is the recipient of the AVMA Council on Research Award in 1994 for excellence in equine research. She has been involved with research on hyperkalemic periodic paralysis in horses since 1985.