Hyperkalemic Periodic Paralysis (HYPP)
What is HYPP?
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. Hyperkalaemia, 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 descendants 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 characterised 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.
Causes of 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.
Inheritance and Transmission of HYPP
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 approximately 50% carrying the defective gene (N/H) and approximately 50% will be homozygous carriers (H/H) regardless of the status of the other parent.
Myths about HYPP
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.
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 realise 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.
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.
Helpful Website: www.vgl.ucdavis.edu/services/hypp.php
AAA Ltd’s position on HYPP:
The Australian Appaloosa Association is committed to removing HYPP from our genetics and we have the following rules in place:
Rule 3.6, 1 Hyperkalemic Periodic Paralysis Disease (HYPP)
- All foals bred from horses known to carry the HYPP gene must be tested.
- Foals born after 1st August 2010 that test positive to HYPP N/H or H/H will not be registered with the AAA Ltd.
- Any existing horses registered with the AAA Ltd that have tested or do test HYPP N/H or H/H, must state this fact in ALL advertising pertaining to the horse.
In addition to the above rules, any Horse, Semen or Embryo imported must be HYPP N/N to be eligible for registration with the Association.