Hyperkalemic periodic paralysis (HYPP) is an inherited disease of the muscle which is caused by a genetic defect. In the muscle of affected horses, a point mutation exists in the sodium channel gene and 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 becomes "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 descendents of the American Quarter Horse sire, Impressive. The original genetic defect causing HYPP was a natural mutation that occurred as part of the evolutionary process. The majority of such mutations, which are constantly occurring, are not compatible with survival. However, the genetic mutation causing HYPP produced a functional, yet altered, sodium ion channel. This gene mutation is not a product of inbreeding. The gene mutation causing HYPP inadvertently became widespread when breeders sought to produce horses with heavy musculature. To date, confirmed cases of HYPP have been restricted to descendants of this horse.

Symptoms and Signs of the Disease

Homozygous horses are affected more severely than heterozygous horses. Under ideal management practices, the defective gene does not appear to have adverse effects, but stress and/or increased potassium in the serum can trigger clinical signs of muscle dysfunction. Why some horses manifest severe signs of the disease and other exhibit little or no signs is unknown and currently under investigation. Unfortunately, a horse carrying the defective gene but showing minimal signs has the same chance of passing the gene to future generations as does the affected horse with severe signs.

HYPP is characterized by sporadic attacks of muscle tremors (shaking or trembling), weakness and/or collapse. Attacks can also be accompanied by loud breathing noises resulting from paralysis of the muscles of the upper airway. Occasionally, sudden death can occur following a severe paralytic attack, presumably from heart failure or respiratory muscle paralysis.

Attacks of HYPP can take various forms and commonly have been confused with other conditions. Because of the muscle tremors and weakness, HYPP often resembles exertional rhabdomyolysis ("tying-up" syndrome). "Tying-up" syndrome can be caused by many different circumstances, including exercising a horse beyond the capacity to which it has been trained, as well as nutritional deficiencies and metabolic diseases. A distinguishing feature of HYPP from "tying-up" syndrome is that horses usually appear normal following an attack of HYPP. Horses with "tying-up" syndrome, on the other hand, tend to have a stiff gait and painful, firm muscles of the hind limbs, rump and/or back. "Tying-up" syndrome is also generally associated with some type of exercise. HYPP, by contrast, is not usually associated with exercise, but occurs when horses are at rest, at feeding time, or following a stressful event such as transport, feed changes, or concurrent illness.

Because a horse may be down and reluctant or unable to stand during an HYPP attack, many owners have thought their horses were experiencing colic. HYPP has also been confused with seizures due to the pronounced muscle trembling and collapse. Unlike seizures and other conditions that cause fainting, horses with HYPP are conscious and aware of their surroundings during an attack and do not appear to be in pain. Respiratory conditions and choking have also been confused with HYPP because some horses make loud breathing noises during an 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.

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, canola oil, soybean meal or oil, 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. Due to the high water content of pasture grass, a horse is unlikely to consume large amounts of potassium in a short period of time if kept on pasture. If the horse is experiencing problems on its present diet, it is recommended to feed a diet containing between 0.6% and 1.5% total potassium concentrations.

Several drugs have been used for prevention of clinical episodes of paralysis. Horses have been treated with either acetazolamide (2-4 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. Breed registries have restrictions on the use of these drugs during competitions (some require a veterinary certificate).

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).

During a severe attack of HYPP, emergency treatment from a veterinarian is necessary. For long term therapy, many horses can be managed by exercise and diet control alone. Regular exercise and access to a large paddock or pasture is preferred over stall confinement. Maintain a regular feeding schedule, preferably equally spaced, two to three times per day. Avoid rapid changes in feed, such as bringing a horse off pasture grass and immediately switching to alfalfa hay. Most horses improve when the potassium content in the diet is decreased.

HYPP 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. The trait is inherited from generation to generation with equal frequency; it does not get "diluted" out or skip generations. Breeding an affected heterozygous horse (N/H) to an affected heterozygous horse (N/H) will result in approximately 50% carrying the defective gene (N/H), approximately 25% will be normal (N/N) and approximately 25% will be homozygous carriers (H/H). Breeding an affected heterozygous horse (N/H) to a normal horse (N/N) will result in approximately 50% normal offspring and approximately 50% carrying the defective gene (N/H).

Breeding an affected homozygote (H/H) will result in all offspring carrying the defective gene regardless of the status of the other parent.

Some people have felt that the disease can be diluted out and not carried to distant generations. This is false because an affected horse has just as much chance to pass on the trait as the affected parent which passed the gene to him. Some people also believe the horse will "grow out of it." This is not true. For unknown reasons, attacks of HYPP tend to occur most often at the beginning of intense training and fitting for shows (age three to seven years old). It is important to realize that horses with HYPP are affected for life. It is possible that older horses do not experience the same conditioning stresses as young horses or owners have discovered the best management strategies for the older horses with HYPP.

Some people also think that if a horse does not show any signs up to a certain age, it does not carry the trait. Unfortunately, this is not the case. Once again, horses with HYPP are affected for life. There was a stallion and a broodmare with HYPP who did not show signs of the disease until age eight and 15, and both horses only experienced one isolated attack.

Owners and breeders of affected horses should inform prospective buyers of the management constraints these horses have and the potential for future episodes of HYPP.

Which Horses Should Be Tested for HYPP?

As noted above, the DNA based test for HYPP identifies the specific genetic mutation which we now know exists in descendants of "Impressive". We presently do not know whether different genetic mutations in other bloodlines also cause HYPP, and the DNA test will not identify other such mutations. Further scientific research is required as to other bloodlines. We presently recommend that all descendants of "Impressive" be tested for diagnostic, treatment and breeding purposes.

(these might not be the most recent although they are interesting)
Hypp Comments from APHA.

HYPP
The committee recommended that foals of 2007 and later tracing to the stallion Impressive be required to be parentage verified and, in addition, tested for hyperkalemic periodic paralysis subject to current testing rules.

In addition, foals of 2007 and later testing positive for HYPP (H/H) will not be eligible for registration with AQHA. The committee also supported a recommendation made by the AQHA Executive Committee to commence an education and awareness campaign informing the membership of the effects of HYPP.

The committee did not make a recommendation limiting the registration of HYPP (N/H) horses.

Please note that these are recommendations only. The recommendations will be presented in the general membership meeting Tuesday morning for approval. If approved in the general membership meeting, the recommendations would be presented to the board of directors Tuesday (March 9th) afternoon for a final vote.

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#### I have invested 22 years of my life as a member of the AQHA. I wish to  strongly oppose the HYPP proposal. However, I am not opposed to mandatory  HYPP testing. I think everybody should be well informed that the horse they  are about to purchase or that they own is HYPP positive or negative. I am  very disappointed about the way this matter has been handled by the AQHA.

Where would the American Quarter Horse Association and Industry be today  without Impressive and his progeny? In the December issue of the AQHA Journal  there is a list that reads as follows.
Top Ten Sires of AQHA World Champions: (In the History of the AQHA)
Stallion: Number:
1. Mr. Conclusion 87
2. Zan Parr Bar 32
3. Ima Cool Skip 30
4. Impressive 29
5. Obvious Conclusion 27
6. Kid Clu 24
7. Two Eyed Jack 21
8. Zippo Pine Bar 18
9. Smart Little Lena 15
10. Conclusive 14
Dominate Clu 14
Zips Chocolate Chip 14

If you read through the names, you will notice that 7 of the 10 are descendants of Impressive! And if you pay even closer attention, you will notice that all  7 of these stallions are HYPP N/H. Some people may not agree, but this seems  pretty significant to me! Look at the number one stallion, Mr. Conclusion, he  is 55 world champions ahead of the the next stallion behind him. This IS  significant. And these world champions weren't just accrued in Halter  Classes, they were in all areas of the AQHA Performance Industry.

In light of this information, and believe me there are many more positive  statistics that I don't have time to write, I don't understand why the AQHA is  trying to extinguish the HYPP N/H horses. It seems to me that these horses  are dominating the AQHA show circuit and have proudly become an Industry  Icon. Just because the AQHA proposes to gradually "phase out" these horses,  is absolutely no consolation! The very minute if/and when this rule goes into  effect, these horses will be virtually worthless as the stigma of the rule  will begin to immediately follow them forever. This will, indeed, create  repercussions that will devastate the Quarter Horse and Halter Horse Industry  for many years to come.

I own two HYPP N/H stallions and several HYPP N/H broodmares. The majority of  my broodmare population are HYPP N/N. These horses are my dream. Whether  they are HYPP N/H or N/N has not ever mattered to me. All of my horses are in
good health and spirit. I have never had any problems with my HYPP N/H  horses. But if there are ever any problems, I am educated on how to treat  these episodes.

I think the AQHA should spend their time, efforts, and finances on more  research and education. There seems to be many misconceptions and  misunderstandings present among members today. It seems to me that the  positive impact that these horses have had on the Quarter Horse industry greatly outweighs the negative.

Karna Colby
Voltaire, ND