Equine Sports Medicine

Hyperkalemic Periodic Paralysis (HYPP)

Overview:

Over 20 years ago, a horse called Impressive was winning all the halter classes. Impressive was well-named - he was so strikingly muscled that he never lost a halter class. It is easy to understand why such a grand specimen would be in huge demand as a breeding stallion. And Impressive showed that he had a very important trait as a breeding stallion - he had the ability to pass on his majestically sculptured musculature to his get. It wasn't for quite some years that people started noticing that Impressive's offspring had inherited more than just his looks. For the gift of Impressive's massive muscles came with a far less welcome inheritance - which came in the form of intermittent episodes of weakness, collapse, or even death. When veterinarians found that these attacks were accompanied by a high level of potassium in the blood, the inherited disease was named hyperkalemic periodic paralysis (HYPP). Today, HYPP continues to plague the Quarterhorse industry, although our ability to identify affected individuals, coupled with responsible action on the part of breeders, has helped us to gain control over this genetic, or inherited disease. We have learned much about this disease, yet it persists in the Quarterhorse and horses with Quarterhorse blood, such as Appaloosas, Paints, and Palominos.

HYPP and inheritance

  • What is hyperkalemic periodic paralysis?
    Although we have named the HYPP for the characteristicaly high potassium levels that occur during an attack, HYPP is actually due to a mutation in a gene that governs sodium channels in muscle cells.
  • What is a genetic mutation, and why does it matter that HYPP is a genetic disease?
    Genes carry coded messages to the protein-making apparatus in the body - these proteins become things that are as diverse as muscles, hooves, and microscopic channels in muscle cells. Mutations tend to occur spontaneously in certain individuals - indeed, we all likely will have mutations in our genetic code at some point, but, generally, no outward effect is seen. Occasionally, as with the Impressive mutation, the consequences are enormous. As far as we know, HYPP is only seen in horses that have inherited the gene for the disease Impressive's bloodline. That is why we generally see the disease in Quarterhorses and horses that have Quarterhorse blood, such as Apaloosas, Paints, and Palominos. As fate would have it, not only did Impressive have a genetic mutation for his muscle sodium channel, but he also had an outwardly very desirable trait - his musculature - that resulted in him being a leading sire, thus, by the early 90s, over 50,000 Quarterhorses had Impressive inheritance. So, Impressive's physique was, in a way, a Trojan horse that allowed a huge and consequential flaw to be transmitted to a large number of horses.
  • HYPP in the horse is a dominant trait. Remember that we all receive two copies of most genes - one from our mothers and one from our fathers. With a dominant trait, the mutation only has to be present on one copy of the gene in order for the trait - in this case the disease, HYPP - to be seen. With recessive genes, on the other hand, both genes must have the mutation for the disease to be seen. What are the practical consequences of this? If an HYPP positive horse is bred to an HYPP negative horse, at least 50% of their offspring will have HYPP, and up to 100% of their offspring will have HYPP, depending if the positive horse has inherited the trait from both parents (homozygous) or only from one (heterozygous). It also seems that homozygous horses are more severely affected than heterozygous horses - it may be that with two copies of the abnormal gene, more of the muscle cells are affected.

When a normal horse (N/N) is bred to a heterozygous HYPP horse (N/H), on average 50% of their offspring will be affected with HYPP

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HYPP on a microscopic scale

  • Hyperkalemic periodic paralysis was given its name because the veterinarians initially noted that during attacks, horses had a very high level of potassium in their blood (hyperkalemia). It seemed that horses affected with HYPP had an intrinsic, but intermittent inability to regulate potassium (so it got the name periodic), which sometimes left the horse unable to rise (so it got the name paralysis).
  • What does sodium have to do with high potassium in the blood?
    Sodium is found in very high levels outside of cells (in the blood, ordinarily), whereas potassium is found in very high levels inside cells. The uneven distribution of the electrolytes, sodium and potassium, allow an electrical voltage to be built up. Without this voltage, muscles would be unable to contract, and nerves would be unable to transmit vital signals throughout the body. In the normal animal, the movement of these electrolytes is highly regulated, and, indeed, the movement of sodium is important in triggering the movement of potassium in and out of cells. If sodium and potassium levels are disturbed, the body suffers severe consequences, ranging from abnormal muscle and nerve function, to death.
  • Small disturbances in blood potassium, that would easily be handled by normal horses, trigger the abnormal sodium channels in horses with HYPP. When the sodium channels open, and start to leak sodium, this triggers potassium in turn to leak into the blood stream. Soon, this vicious circle leads to the muscle being first hyperexciteable (that is, it contracts far more easily than normal muscle) and then, as time goes on, the muscle becomes flaccid.
  • What does this mean for the horse?
    At first, the hyperexciteable muscle trembles and contracts more easily. As more and more potassium floods into the bloodstream, the muscles eventually become unable to contract, and the horse is effectively paralyzed.

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What are the signs of an HYPP attack?

  • As with any genetic disease, HYPP has different degrees of what is termed penetrance in different horses. Penetrance is a term that is used to describe the extent to which a genetic trait can be seen in a particular individual. Some horses will be severely affected (and this will be exacerbated if they are homozygous for the trait), and others may look normal for the majority of their lives.
  • Signs that you may see during an attack of HYPP are:
    • Muscle trembling
    • Prolapse of the third eyelid - this means that you may note the third eyelid flickering across the eye, or covering more of the eye than normal
    • Generalized weakness
    • Weakness in the hind end - the horse may look as though it is 'dog-sitting'
    • Complete collapse
    • Abnormal whinny - this is because the muscles of the voicebox are affected as well as other muscles

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What diseases could be mistaken for HYPP?

  • When HYPP was first seen in horses, it was often confused with:
    • Tying Up Syndrome
    • Seizures
    • Cardiac problems
    • When a horse is having an attach of HYPP, he usually remains very alert - this helps us to distinguish HYPP from a seizure, in which the horse is not aware of who or where he is.
  • After an HYPP attack is over, the horse appears normal - he does not show signs of stiffness or muscle pain. This helps us to distinguish HYPP from Tying Up Syndrome, which is characterized by painful, stiff muscles that may last for days to weeks after an episode. The horse often sweats profusely, and appears to be painful. Tying Up Syndrome is also accompanied by high muscle enzymes, such as CPK. This is because muscle cells are actually breaking down. A horse having an HYPP attack will have normal muscle enzymes. HYPP attacks can also occur at any time - even when a horse is standing quietly in his stall. Tying Up Syndrome is usually precipitated by exercise.
  • Cardiac abnormalities severe enough to cause collapse are usually accompanied by other signs of cardiac failure, such as weakness, abnormal jugular pulsations, or peripheral edema - even when an attack is not occuring. These horses will also often have murmurs or cardiac arrhythmias - this is not seen with HYPP unless the horse has more than one problem.

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How does my veterinarian make a diagnosis of HYPP?

  • In addition to the clinical signs, if your veterinarian is able to obtain a blood sample at the time of an attack, analysis will show a very high potassium level. Blood potassium levels are usually normal in between.
  • Veterinarians used to diagnose HYPP by challenging the horse with a test dose of potassium given orally. This test is generally no longer done. Why? Well, it did give us some false negatives, meaning that the test would say that a horse was not affected when it actually was. It also was a rather dangerous test - horses stood a risk of having a severe episode of HYPP because of the test.
  • There are also specialized neurodiagnostic tests that can help to confirm a diagnosis of HYPP. For instance, although we don't see outwardly abnormal signs during an attack, the muscles are actually still functioning abnormally. This is detectable using an electromyogram, or EMG. This test usually must be done in a referral hospital that has specialized equipment. What the examiner will notice is that the muscle has abnormal spontaneous activity, due to small fluctuations in potassium and sodium.
  • The definitive test, however, is a genetic test that allows us to determine whether the affected horse carries the gene for HYPP. All that this requires is a blood sample - and it is a very accurate test.

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How can my horse be treated if he has a severe attack?

  • It is important to be able to recognize whether your horse is having a mild attack or a severe attack. A moderate to severe attack requires veterinary care, whereas a mild attack may often be treated at home by the owner. If you are not experienced with this disease, it is wise to call your veterinarian in all cases, until both of you feel comfortable with your ability to make the right decision.
  • A mild attack would consist of mild muscle trembling, but no signs of recumbency, abnormal whinny, or generalized weakness.
  • In the case of a mild attack, there are several things that seem to help.
    • Very light exercise - this means hand-walking, not barrel racing!
    • Get some carbohydrates into your horse - plain corn, light corn syrup, or even sugar will help. Avoid feeds with molasses added, as molasses is high in potassium. Sugar prompts the body to release insulin, which in turn has the effect of moving potassium back into the cells.
    • If you have already consulted with your veterinarian about your horse, she may recommend that you give your horse a dose of a drug called acetazolamide. This is a diuretic (makes your horse urinate) that also promotes the loss of potassium in the urine.
  • In the case of a moderate to severe attack, emergency treatment by a veterinarian is needed.
  • The goal of treatment is to decrease the amount of potassium in the blood stream - only by doing this will the muscles regain their ability to contract normally.
  • What can your veterinarian do to reduce the blood potassium?
    • One of the first things that your veterinarian will do is to give your horse dextrose (a sugar) intravenously. As with oral adminstration of sugar, this will help to drive potassium back into the cells.
    • Oftentimes, your veterinarian will combine the dextrose with bicarbonate, which has an additive effect with the dextrose.
    • If your horse is severely affected, your veterinarian may administer calcium intravenously - this may help to counter the effects of the potassium.
    • If none of this is helping, your veterinarian may choose to give insulin to boost what your horse is producing on its own in response to the dextrose.
    • Finally, your veterinarian will probably give acetazolamide, to encourage your horse's body to waste potassium.

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How can I prevent attacks of HYPP?

  • Many people keep HYPP-positive horses on acetazolamide all the time. It seems to have little adverse effects on the horse, and is relatively inexpensive. Most owners of HYPP horses report that this reduces the number and severity of attacks.
  • It is sensible to keep your horse on a low potassium diet.
  • Foods that are very high in potassium include:
    • Molasses
    • Alfalfa and timothy hay
  • Foods that are low in potassium include:
    • Most grains (but avoid sweet feed, that is mixed with molasses)
    • Oat hay
  • Make sure that your horse has a regular exercise schedule - if you are not going to ride your horse one day, make sure that he has plenty of turn-out. In general, turnout with good shelter from the elements is a better housing choice for these horses than being confined to a stall.
  • Avoid sudden exposure to extremes of heat or cold
  • Maintain a regular feeding schedule. High potassium hays such as alfalfa and timothy are more likely to precipitate an attack if they are suddenly introduced into a previously low potassium diet.
  • Feed at least three small grain meals (such as oats, barley, or corn) per day.

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Now that we know about the inheritance of HYPP, can we eliminate it?

  • Well, the problem is that horses with the gene for HYPP tend to be highly muscled, with the ideal physique for a show Quarterhorse. Because this desireable look accompanies the defect, people will still want to breed these horses for show. The only way that this disease will every be entirely eliminated is if all owners have their horses genetically tested before breeding AND agreeing not to breed horses who are positive for the HYPP gene.

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Summary:

  • HYPP is an inherited disease in Quarterhorses and horses with Quarterhorse blood who are descended from the stallion, Impressive.
  • HYPP is inherited as a dominant trait, so even if only one parent is affected, the offspring can be affected
  • HYPP is due to a mutation that causes an abnormal sodium channel in muscle cells
  • This mutation results in an abnormal level of blood potassium
  • Abnormal blood potassium levels cause the muscles eventually to be unable to contract
  • HYPP can often be managed with careful feeding and exercise regimens.
  • Clinical signs of HYPP include muscle trembling, weakness, collapse, and abnormal whinnying.
  • Mild episodes of HYPP can often be managed by owners, but moderate to severe attacks require emergency veterinary treatment.
  • Because HYPP is an inherited disease, the only way to eliminate it from the population is to test all breeding horses - those that are positive should not be bred.