Hyperkalemic Periodic Paralysis: 14 Years Later

Sharon Spier, DVM, Dipl. ACVIM, PhD, associate professor at the University of California, Davis, has pioneered much of the research on HYPP. She presented updated information gleaned over the past 14 years on this disease at the 2006 AAEP Convention.

The syndrome was identified in the 1980s in descendants of the Quarter Horse stallion Impressive. It was noted that HYPP particularly seemed to affect young, well-muscled Quarter Horses, Appaloosas, Paint horses, or crosses with this lineage, leading researchers to look for a genetic link. They found a genetic defect that affects conductivity of muscle membranes, resulting in persistent muscle contraction.

Diagnostic testing for HYPP (on tail and mane hairs) has been available since 1992, and it can distinguish among homozygous-affected (H/H), heterozygous-affected (H/N), and normal (N/N) horses. (Homozygous horses, which have a double copy of the defective gene, are far more severely affected than heterozygous ones.)

In 1996 the American Quarter Horse Association (AQHA) officially declared HYPP as an undesirable genetic defect, and it established mandatory testing for all foals born after Jan. 1, 1988, descending from Impressive. Just a couple of years ago, it was mandated that any foal born in or after 2007 that tests H/H cannot be registered.

The clinical signs and onset are variable; most affected horses do have clinical signs, while a few horses with the mutation will appear normal. An affected horse has intermittent attacks of weakness, muscle tremors, and/or paralysis and recumbency that can last from minutes to hours. In some cases a paralytic episode might persist longer than 24 hours and the horse might require slinging with a large animal lift. Many horses remain standing during an episode; some might sway or stagger, while others dog sit due to hind limb weakness.

Other signs include elevated heart rate, prolapse of the third eyelid, abnormal respiratory noises, and sweating; yet the horse remains bright and alert, albeit anxious. A horse can die from respiratory or cardiac paralysis.

An attack is not necessarily precipitated by anything definable such as exercise, although high-potassium feeds and/or stress situations readily precipitate an episode. A foal might demonstrate clinical signs early on, including an inability to nurse or swallow due to partial or complete laryngeal paralysis. Such a foal will make a high-pitched wheezing noise that accompanies respiratory distress.

An HYPP-affected horse appears normal between episodes, with normal laboratory findings. Veterinarians have found if affected adult horses are managed carefully through diet and exercise, many can live relatively normal lives.

During an HYPP episode, laboratory tests show blood concentration and high circulating serum levels of potassium, with muscle enzymes ranging from normal to slightly increased. Muscles remain abnormal even between bouts of symptoms, maintaining some degree of excessive tone. Electromyography demonstrates that all muscles are affected.

The actual genetic mutation that causes HYPP involves a defect affecting a protein that is called the voltage-gated sodium channel. This channel is a tiny gateway in the membrane of a muscle cell that controls the movement of sodium particles in and out of the cell. These particles have a charge that changes the voltage current of the muscle cell. The current allows the cell to contract or relax.

In HYPP horses, the channel's regulation of the particles sometimes fails, and this disrupts the normal flow of sodium in and out of the cell. During episodes, uncontrollable twitching or complete muscle failure can result, as can potassium leakage into the bloodstream.

At UC Davis Spier tested samples submitted by Quarter Horse owners for HYPP testing in 1992-1996 and found that 1.1% had the H/H homozygous genotype, indicative of disease, while 35% were heterozygous affected (N/H). Results of testing in 2005 indicated that 2.2% of horses tested had the H/H genotype, and 37% were N/H. (N/H horses are affected with the disease and have a 50% chance of producing a foal that is HYPP positive.)

What is particularly striking is that in the past 14 years of genetic testing, not only has the HYPP gene frequency not decreased, but there has been a two-fold increase in the number of horses with this homozygous gene frequency.

Breeders continue to be "rewarded" for this defect since HYPP horses of Impressive descent tend to be heavily muscled, a trait that is considered desirable in the halter horse show ring. It is possible that constant muscle stimulation from the disease itself leads to muscle definition and tone that is visually favored. Thus far, 4% of Quarter Horses are affected; meaning that approximately 160,000 individuals have this disease.

HYPP can be controlled and managed to some degree with diet by eliminating or limiting high-potassium feeds or supplements containing alfalfa hay, soybean products, molasses, electrolytes, or kelp. Dietary potassium should be kept below 1½% of the horse's daily nutritional intake. Fasting periods should be minimized, as should stressful events such as trailering.

Anytime a horse will be sedated or undergo general anesthesia, the owner must warn the veterinarian of a horse's HYPP condition. An owner might avoid an attack by administering corn syrup or grain to provide sugar that drives potassium back into the muscle cells, and by lightly exercising the horse. A veterinarian might also implement intravenous medical treatment with calcium and dextrose to elevate calcium levels and decrease membrane hyperexcitability. He or she also might give other medications to increase potassium excretion in urine and stimulate insulin secretion to drive potassium into the cells.

Get research and health news from the American Association of Equine Practitioners 2006 Convention in The Horse's AAEP 2006 Wrap-Up sponsored by OCD Equine. Files are available as free PDF downloads.

About the Author

Nancy S. Loving, DVM

Nancy S. Loving, DVM, owns Loving Equine Clinic in Boulder, Colorado, and has a special interest in managing the care of sport horses. Her recent book, All Horse Systems Go, is a comprehensive veterinary care and conditioning resource in full color that covers all facets of horse care (available at Shop.TheHorse.com or by calling 800/582-5604). She has also authored the books Go the Distance as a resource for endurance horse owners, Conformation and Performance, and First Aid for Horse and Rider in addition to many veterinary articles for both horse owner and professional audiences.

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