HYPP: Hyperkalemic Periodic Paralysis

They gave the muscular Quarter Horse colt an ambitious name: Impressive. He lived up to the name in such dramatic fashion that it became a household word in Quarter Horse circles - especially among breeders and exhibitors involved in showing halter horses.

Impressive sons and daughters were big, bold, and beautiful with defined musculature. They took the halter show ring by storm, racking up championships from one part of the country to another. Just as quickly, sons and daughters of the great stallion were in demand for breeding programs.

Then, the Impressive ship hit the sand.

A number of owners of Impressive offspring and second- and third-generation descendants of the stallion reported that some of these horses seemed to have acquired a muscle disease. Some would exhibit muscle tremors and with others there was even paralysis.

Enter Sharon Spier, DVM, PhD, an associate professor of the Department of Medicine and Epidemiology at the University of California, Davis. Spier led the effort by researchers to find out more about the disease and what caused it. The project began in 1989 and was funded by the American Quarter Horse Association.

The results of that research produced a bombshell for the Quarter Horse industry. Spier and her associates reported that the disease involved was Hyperkalemic Periodic Paralysis, known industry-wide today by the acronym HYPP.

Merely identifying the disease and the way it functioned, however, was not the bombshell. The bombshell came when it was reported that every single horse found with the disease traced to one stallion--Impressive.

The researcher's report was published in the September 1992 issue of The Quarter Horse Journal, but Impressive was not identified by name. In the months that followed, there were rumors, speculation, and widespread concern within the industry.

The AQHA issued an official statement in the December 1992 issue of the Quarter Horse Journal, but it only fueled the flames. The statement said only that the disease affected a small percentage of the total horses registered by AQHA, and that it appeared to be limited to individuals from one bloodline. It further said that most of the individuals affected were bred for halter competition.

That issue of the magazine had already gone to press when Spier appeared on the program Nov. 30, 1992, at the annual convention of the American Association of Equine Practitioners. In answer to a question that followed her presentation on HYPP, she identified Impressive as the only bloodline that carried the mutant gene which causes HYPP.

The issue was now out in the open, and the Quarter Horse industry began to grapple with it. By the time research traced the disease back to him, Impressive had been siring foals for the better part of two decades, and his many descendants, now into the second and third generations, had become the mainstays of numerous breeding programs. Approximately 100,000 horses today carry the name Impressive in their pedigrees.

What is this disease that threatens to overshadow the show ring breeding legacy of such a great horse?

Spier has described it thusly:

"Hyperkalemic Periodic Paralysis is a muscular disease that affects both horses and humans. It is caused by a hereditary genetic defect that disrupts a protein called a sodium ion channel, a tiny gateway in the membrane of muscle cells. The genetic defect disrupts the channel's normal opening and closing, such that uncontrolled sodium influxes occur. These influxes, in turn, change the voltage current of muscle cells, causing uncontrolled muscle twitching or profound muscle weakness. High levels of potassium in the blood usually are present when the disruptions in the ion channel occur.

"Horses with HYPP can experience unpredictable attacks of paralysis which, in severe cases, can lead to collapse and sudden death. The cause of death usually is cardiac arrest and/or respiratory failure. The disease is characterized by intermittent episodes of muscle tremors manifested by generalized or localized shaking, trembling, and weakness.

"Occasionally, episodes are accompanied by respiratory noises resulting from paralysis of the muscles of the upper airway (larynx and pharynx). In cases of mild attacks, muscle tremors may be so subtle as to be detectable only by an experienced clinician performing EMG testing."

The disease, Spier further reported, was caused by a mutant gene.

"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."

There is a bit of good news amongst all this. Spier and her associates made history when they were able to identify HYPP with DNA testing. HYPP is the first genetic disease that can be identified by a DNA test, and it is extremely reliable.

The American Quarter Horse Association, which struggled with how best to handle the disease in the early going, has now taken firm and definitive steps aimed at identifying and controlling it.

Following the 1996 AQHA convention in Seattle, Bill Brewer, executive director, announced the new rules set forth by the association's board of directors.

He had this to say:

"Beginning with the 1997 AQHA Official Handbook, HYPP will be listed in rule 205 among conditions commonly considered undesirable traits or genetic defects, such as parrot mouth or cryptorchidism. These conditions do not prevent a horse from being used as breeding stock or from participating in AQHA-approved events, subject to rules of the individual event.

"Beginning with 1998 foals, the rule requires the following notification to be placed on the registration certificates of foals descending from any bloodline determined to carry the HYPP gene: 'This horse has an ancestor known to carry HYPP, designated under AQHA rules as a genetic defect. AQHA recommends testing to confirm presence or absence of this gene.' "

Beginning in 1999, AQHA will test all foals that trace to Impressive for HYPP. The testing will be required prior to the foals being registered.

However, if the parents have tested negative for HYPP, the testing of the offspring might not be required.

Because HYPP is inherited as an autosomal dominant trait, it can occur in both males and females and is inherited from generation to generation with equal frequency. It does not get diluted out in succeeding generations.

In four years of testing for genetic mutation between October of 1992 and 1996, more than 27,000 samples were tested for HYPP. Of that group, 63% were normal (NN), 36% were heterozygous for HYPP (NH), and 1% were homozygous (HH).

Being heterozygous means the horse carries one copy of the HYPP gene. Being homozygous means the horse carries two copies of the gene.

Breeding an affected heterozygous horse to a normal horse, says Spier, will result in approximately 50% normal offspring, while 50% will carry the defective gene. Breeding an affected homozygote will result in all offspring carrying the gene mutation, regardless of the status of the other parent.

Normal negative offspring can be safely bred without fear of HYPP being inherited, unless, of course, they are bred to a horse that is positive. Thus, selective breeding of normal, negative horses to others that are also negative could entirely eliminate HYPP.

How can researchers be so sure that only the Impressive bloodline carries the mutant gene? First, they will only say that to date they have not found the troublesome gene in any other bloodline. However, one study pretty much solidified the already existing evidence.

Stored blood samples from 6,000 horses received between January of 1989 and December of 1991 that were on file in conjunction with blood-typing requirements of AQHA were available at the Veterinary Genetics Laboratory at the University of California, Davis. All samples were from horses bred and foaled before the availability of a genetic test for HYPP.

Following is the researcher's report:

"We used a computer program to choose, at random, 1,000 samples from the 6,000 available to test for the HYPP gene mutation. The samples were primarily from breeding stallions, but were otherwise not selected for bloodlines. Among the 1,000 samples, 22 were Thoroughbred (16 males and six females) and 978 were from Quarter Horses (882 males and 96 females). The foaling year with the largest number of tested horses was 1983 (109 horses).

"Forty-three horses (42 males and one female) tested positive for a single copy of the HYPP gene. No homozygotes were detected. All of the positive horses were Quarter Horses and all traced to the stallion Impressive as first-, second-, or third-generation descendants...

"The first foaling year with an HYPP-positive horse was 1977. The foaling years with the highest frequency of HYPP positives occurred between 1984 and 1987, for which the average frequency of positives per year over those four years was 10%.

"Among the 1,000 tested horses, 100 traced by pedigree to the stallion Impressive. All of the N/H (heterozygous) horses were Quarter Horses and all traced to Impressive as first-, second-, or third-generation descendants.

"This information provides substantial evidence to confirm that Impressive is the major, if not only, pedigree source of the HYPP gene in Quarter Horses, as proposed in previous studies...

"The overall frequency of HYPP positive among the Impressive subset was 43%. This frequency is much higher than expected if breeding stock is randomly selected with respect to HYPP from pedigrees tracing to impressive.

"It is in the range of values expected, for example, from a set of matings in which one parent in every breeding pair was N/H. Since the majority of horses in this sample set that traced to Impressive were second- or third-generation descendants, for which only 50% or 25%, respectively, of breeding pairs could be expected to have one parent positive for the trait, the frequency of HYPP-positive horses is clearly higher than expected.

"From these data, we conclude the HYPP gene is infrequent among registered Quarter Horses, although its occurrence is substantially linked to pedigrees tracing to Impressive."

Unfortunately, horses do not outgrow HYPP. They are affected for life, but it does appear that symptoms might decrease with age. The disease also appears to be associated with periods of stress, such as being hauled, intensive training, dietary changes, illness or disease, general anesthesia, or the beginning of a training program which changes the afflicted horse's normal lifestyle.

Spier and her associates maintain, however, that HYPP in horses can be managed and incidents of mortality significantly reduced by proper diet and the administration of medication. It is their belief that horses afflicted with HYPP, if properly managed, can lead productive, useful lives.

The first step, obviously, is to have the disease properly diagnosed via the highly reliable DNA test. At present five laboratories  meet AQHA requirements for conducting the test--University of California, Davis, the Oklahoma Blood Institute, Shelterwood Labs, Mann Equitest Labs, and NWS Agriculture. Contact the AQHA at 806-376-4811 for a request form for a hair collection kit. The AQHA no longer uses blood samples for testing. The test costs $35.

Following are management practices suggested by researchers that will assist in the control of HYPP:

1. Establish a regular feeding and exercise schedule. Avoid fasting and water deprivation. Horses do better if allowed access to a paddock or pasture rather than strict stall confinement. Daily or nightly turnout is helpful.

2. Adult horses do very well on grass or oat hay alone or pasture. If it is necessary to use alfalfa to balance the ration for growing horses, then mix alfalfa with grass hay or oat hay and grain (oats are best) to decrease potassium content of diet. Feed equal amounts of hay and grain two or three times daily. Avoid rapid changes in diet. Provide access to a white salt block or feed loose salt.

3. Administer acetazolamide (Diamox), a diuretic (2 mg/kg orally twice a day). Many halter horse owners continue alfalfa hay as the only roughage, but maintain their horses on this drug for all or most of their lives. (Please note, the researchers caution, that
acetazolamide is a forbidden substance under AQHA and AHSA regulations.)

4. Inform your veterinarian of HYPP condition prior to any general anesthesia, which might precipitate an episode of paralysis. Maintain acetazolamide therapy before and after surgery or anesthesia.

5. Use common sense while hauling. Be sure to stop and water horses frequently (every two hours).

The researchers also have suggestions for dealing with a horse which suffers a mild attack (when the horse is not down, but has muscle tremors). One or more of the following emergency treatments are recommended for mild attacks:

1. Exercise the horse, either by walking or longing. Exercise stimulates adrenaline, which helps replace potassium inside cells. However, one should use caution as the horse could stumble and fall while having muscle tremors.

2. Feed grain (oats, dry corn-oats-barley, or light Karo syrup) for glucose supplement. Feeding carbohydrates supplies glucose, which stimulates the release of insulin and promotes potassium uptake by cells.

3. Administer acetazolamide orally (3 mg/kg). This usually means six to eight tablets if the tablets are 250 mg each. Acetazolamide increases potassium excretion from the kidney and also affects glucose metabolism.

For severe attacks, the immediate procedure is obvious--call the veterinarian.

Another basic question surfaces: Is it dangerous to ride a horse known to carry the HYPP gene? After all, it already has been determined that episodes of weakness or paralysis are unpredictable.

Research on this subject also was carried out at the University of California, Davis. Nine horses, five of which had tested positive as heterozygous carriers of HYPP and four which were negative, completed four exercise trials using a high-speed treadmill at both aerobic and anaerobic intensities. The tests were carried out with and without the use of acetazolamide therapy.

The near-maximal exercise test consisted of a warm-up followed by two minutes of strenuous galloping. The submaximal exercise test consisted of 30 minutes of slow trotting at 60% maximal effort as determined by measurements of heart rate.

The results were upbeat, even though three of the five horses had episodes of muscle tremors during the rest period following exercise.

Here is what the researchers said:

"From this study, we can advise owners of affected horses that the chance of a paralytic episode occurring while the horse is being exercised appears unlikely.

"However, we did observe episodes of muscle tremors in the rest period after exercise. We recommend that only persons experienced with the symptoms handle and ride affected horses, and to use caution if any abnormal clinical signs are observed. Acetazolamide therapy decreased the appearance of clinical signs following exercise in two of the three horses which had episodes of muscle tremors during the rest period."

The researchers have done their part and are continuing to do it. They have identified the disease and have come up with a nearly foolproof test to determine whether a horse carries the mutant gene. They have also established procedures for dealing with afflicted equines so that they can be useful throughout their lives.

The rest is up to the breeders and owners of these afflicted horses. If they carry out sound breeding programs that do not include breeding HYPP carriers, the disease will be eradicated and Impressive-line horses which are free of HYPP can continue to shine and proliferate.

About the Author

Les Sellnow

Les Sellnow is a free-lance writer based near Riverton, Wyo. He specializes in articles on equine research, and operates a ranch where he raises horses and livestock. He has authored several fiction and non-fiction books, including Understanding Equine Lameness and Understanding The Young Horse, published by Eclipse Press and available at www.exclusivelyequine.com or by calling 800/582-5604.

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