Hyperkalemic periodic paralysis (HYPP)

What is HYPP?

Takeaways

• HYPP is a muscular disease caused by a known genetic mutation with an autosomal dominant mode of inheritance.
• Affected horses can exhibit signs that include muscle tremors, weakness, paralysis and collapse.
• The signs of HYPP can be confused with other diseases and conditions. A DNA test is available to confirm a diagnosis.

HYPP is a muscular disease caused by a genetic mutation that disrupts the sodium ion channel and results in an excessive amount of potassium in the blood (hyperkalemia). This causes the muscles to contract more readily than normal. Horses with HYPP can experience unpredictable attacks of muscle tremors or paralysis, which in severe cases can lead to collapse and sudden death due to cardiac arrest or respiratory failure. HYPP is primarily associated with horses with heavy musculature (although not necessarily all well muscled horses are affected).

HYPP has an autosomal dominant mode of inheritance, meaning that only one copy of the mutation is needed to produce the disease and it can occur in both males and females. A genetic test is available to help manage breeding decisions and avoid producing affected offspring.

What are the clinical signs of HYPP?

Affected horses can exhibit a range of clinical signs. Horses with two copies of the genetic mutation (homozygous) are usually more severely affected than horses that only have one copy (heterozygous). Some affected horses show no signs at all or will only have one or two episodes in their lifetimes. In other cases, especially when under stress, increased potassium in the blood can trigger clinical signs. The duration of clinical signs can also vary from minutes to hours. It is currently unknown why some affected horses show severe signs of disease whereas others exhibit few or no signs.

HYPP is characterized by muscle tremors, weakness, paralysis, and collapse. Attacks are sporadic and can be accompanied by loud breathing due to paralysis of airway muscles. Sudden death can occur due to heart failure or respiratory muscle paralysis.

The signs of HYPP are sometimes confused with other conditions such as rhabdomyolysis (“tying-up”), colic, seizures and choking. Horses with HYPP appear normal after an attack whereas horses that have tied-up have stiff, firm muscles and a painful gait for an extended period. During an attack, horses with HYPP are conscious, aware of their surroundings, and do not appear to be in pain.

Environmental factors including stress, dietary changes, fasting, general anesthesia, illness and changes in exercise can cause attacks of muscle weakness in affected horses.

How is HYPP diagnosed?

Horses that exhibit clinical signs and are descendants of the stallion “Impressive” on either the sire or dam’s side are highly likely to be affected with HYPP. A DNA test is performed to verify that a horse has HYPP. Hair samples (with the roots attached) can be submitted to the UC Davis Veterinary Genetics Laboratory. Results are typically returned within a week and will indicate how many copies of the “normal” (N) gene and how many copies of the HYPP mutation (H) are identified. N/N horses are unaffected; N/H horses are heterozygous for HYPP; H/H horses are homozygous for HYPP and may be more severely affected.

How is HYPP treated?

For a mild HYPP attack (the horse exhibits muscle tremors but remains standing):

• Contact your veterinarian.
• Exercise the horse by walking or longeing, using caution and being aware that the horse could stumble and fall.
• Feed dry grain (oats, corn, barley) or lite Karo syrup (60-120 mLs orally).

Episodes of HYPP can usually be controlled with appropriate nutrition and management. This can include:

1. Avoiding high potassium feeds such as alfalfa hay, brome hay, soybean meal, sugar molasses and beet molasses. Optimally, later cuts of Timothy or Bermuda grass hay and grains such as oats, corn, wheat, barley, and beet pulp should be fed in small meals several times a day.   Pasture works well for horses with HYPP because the high-water content of pasture grass makes it unlikely that horses will consume large amounts of potassium in a short period. Ideally, horses with recurrent episodes of HYPP should be fed a balanced diet containing between 0.6% and 5% total potassium concentration and meals containing less than 33 g of potassium.  Many horses may be asymptomatic on diets containing higher concentrations of potassium.  Horses take about two weeks to adapt to diets higher in potassium. A more stabilized blood potassium concentration decreases the frequency of clinical signs. 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.  Supplement with vitamin E, selenium, salt and balanced minerals where indicated to meet nutritional requirements. Commercially available complete feeds with a guaranteed potassium content may be more convenient in some cases.
2. Allowing frequent access to turnout and/or exercising regularly.
3.  Avoiding rapid changes in feed.
4. Drugs, including acetazolamide or hydrochlorothiazide, have been used successfully to prevent clinical episodes in some cases. However, it is important to note that breed registries and many equestrian associations have restrictions on the use of some of these drugs during events and competitions.

Severe HYPP attacks require emergency veterinary treatment.

What is the prognosis for HYPP?

Horses with HYPP are affected for life, but most improve under appropriate management that includes decreased potassium in the diet. Long term, many horses can be managed by diet and regular exercise and have successful careers. It is unlikely that a horse will have a paralysis episode while being ridden, but these episodes are unpredictable. As such, affected horses are not suitable for young or inexperienced riders and should only be handled by experienced riders who are aware of the signs and familiar with the particular horse’s behavior.  Both heterozygotes (N/H) and homozygotes (H/H) are susceptible to episodes of collapse, although homozygous (H/H) horses are more severely affected (more frequent episodes of tremors or collapse) than heterozygous (N/H) horses.

It is important to inform your veterinarian of your horse’s HYPP status prior to general anesthesia, as this can trigger an attack of paralysis.  Horses with HYPP may be anesthetized or sedated for procedures, but the veterinarian should be prepared to administer intravenous calcium in fluids if necessary to treat an episode.  Avoid long periods of fasting if possible.

How can HYPP be prevented?

Breeders can avoid producing affected offspring by utilizing the available genetic test. Expected breeding outcomes are shown in the tables below. N = normal copy of the gene, H = copy of the HYPP disease gene. Breeding an affected homozygous horse will result in all offspring carrying at least one copy of the disease mutation regardless of the status of the other parent.

Breeding outcomes for parents that each have one copy of H.

 

Breeding outcomes for one unaffected parent and one parent with one copy of H.

For more information:

UC Davis Veterinary Genetics Laboratory HYPP DNA testing

What’s the Hype Over HYPP? By Dr. Sharon Spier and the American Association of Equine Practitioners

UC Davis Center for Equine Health Horse Report, January 2006

UC Davis Center for Equine Health Horse Report, January 2005

*This article may not be reproduced without the written consent of the UC Davis Center for Equine Health. Please email requests to cehadmin@ucdavis.edu.