Hyperkalemic Periodic Paralysis Page 1

Hyperkalemic Periodic Paralysis (HYPP):

Biology, Genetics, & Care

Paula Buehrer

BIO 410, Fall Semester

Sr. Marya Czech, SND, MA

November 28, 2005

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ABSTRACT

Hyperkalemic Periodic Paralysis (HYPP) is a genetic mutation in the sodium ion channel

that occurs in the descendants of a single quarter horse stallion – Impressive. The genetic

mutation occurred as a point mutation of the alpha subunit in the voltage gated sodium ion

channel of the SCN4A gene. The mutation impairs the rapid inactivation of the sodium ion

channel affecting the protein in the cell membrane resulting in an abnormal opening and closing

of the channel. This results in potassium leaking into the bloodstream and elevated serum

potassium levels which affect the skeletal muscle tissue triggering muscle fasciculation,

recumbency, dog sitting, sweating, and the inability to rise for an extended period.
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TABLE OF CONTENTS

Abstract………………………………………………………………………………….page 2

Where the Condition Started……………………………………………………………page 4

First Clinical Signs Recognized…………………………………………………………page 5

The Condition is Named…………………….………………………………………….page 6

What Are Sodium Ion Channels?………………………………………………………page 6

Figure 1. Na – K ATPase The Sodium-Potassium ATPase pump……………….page 7

How Do Ion Channels Work?………………………………………………………….page 8

The Function of a Mutated Ion Channel……………………………………………….page 9

The Genetics of the Mutation………………………………………………………….page 9

Hereditary Traits………………………………………………………………………page 11

Figure 2 Distribution of the HYPP………………………………………………page 12

Clinical Symptoms……………………………………………………………………page 13

Treatment For the Condition…………………………………………………………page 14

What Are the Triggers of an Episode?……………………………………………….page 15

Diet and Maintenance of Affected Horses……………………………………………page 15

Medical Considerations………………………………………………………………page 17

In Conclusion…………………………………………………………………………page 18

Steps Toward Progress……………………………………………………………….page 19

Works Cited………………………………………………………………………….page 23
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WHERE THE CONDITION STARTED

It is hard to believe the magnitude that a single stallion and his genetic contribution could

have on, not one but several breeds within the entire equine species. How could one horse

contribute one of the most recognizable genetic mutations in the history of equine science on

such a large scale to so many within the species? The how is easily answered by the fact that the

American Quarter Horse stallion Impressive was just that, impressive. He personified the

stereotypical perfect quarter horse. He had conformation, muscle and beauty. In the halter show

pen he was the standard by which all other horses were judged.

Impressive was foaled in 1969 on a farm in Ohio. His sire Three Bars, a thoroughbred,

and his dam a quarter horse name Glamour Bars; he was bred to be a racehorse. As a two year

old he was broke to ride and sent to the track, but was so muscular he was never raced. Instead

he was sent to the show ring where he went on to achieve a very distinguished show career. In

31 attempts in the halter arena he won 31 times, gained 20 grand championships and was the first

World Champion Aged Stallion in the AQHA winning the title in 1974 (Steward).

Because of his superior conformation, excellent musculature, and impressive show

record, he became a very sought after sire not only by quarter horse breeders but also those who

bred appaloosas and paints for show at halter as well. Many of his offspring inherited their sires’

sensational physical qualities making them outstanding horses in the show pen. Offspring of

Impressive went on to become prominent and productive broodmares and stallions. By 1992, 13

of the top 15 horses on the leading sires list were descendants of Impressive who was also fourth

on the same list. It is estimated that more than 55,000 registered Quarter Horses, Paints, and

Appaloosas around the world are descendents of Impressive (Moore).

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FIRST CLINICAL SIGNS RECOGNIZED

Owners of foal from Impressive’s first foal crop began noticing an unusual twitching in

the muscles of some of his prodigy. The associated condition had not yet been identified as a

disease in equines – humans suffer from a genetic defect by the same name- so the phenomenon

was usually diagnosed as one of any number of other equine ailments. The episodes did not have

a consistent etiology and varied in length and severity making diagnosis difficult. Some horses

possessing the yet to be identified gene were unable to move or simply collapsed for no apparent

reason (Moore).

When numerous individuals presenting symptoms of this unknown condition were

reported among the quarter horse population, it quickly became a concern of the American

Quarter Horse Association. In 1989 the organization funded a project at the University of

California, Davis to investigate this medical phenomena. In September of 1992 the results of the

UC, Davis research project were printed in the Quarter Horse Journal and the strange muscle

tremors were finally given a name - Hyperkalemic Periodic Paralysis, or HYPP as it is now

commonly referred to. Speculation, concern, and rumors regarding the condition proliferated

prompting the AQHA to make an official statement of position. The statement acknowledged

that only a small percentage, less than 1%, of the total number of horses registered by the AQHA

was affected and that those affected seemed to originate from a single bloodline. It also stated

that most of the affected individuals were bred for one purpose - halter competition. The specific

bloodline was not mentioned in the statement (Unknown 51).

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THE CONDITION IS NAMED

In a December 1992 meeting of the American Association of Equine Practitioners

(AAEP) Dr. Sharon Spier of UC, Davis, one of the lead researcher’s on the AQHA funded

project, revealed the stallions name while being questioned following her presentation on HYPP.

Dr. Spier acknowledged that all horses found with the disease, during her research, descended

from one single quarter horse stallion. In the January 1993 issue of the Quarter Horse Journal,

the stallions name was released to the public in the "AQHA Update" article. Impressive’s name

was now associated with this perplexing medical condition. With the proverbial cat out of the

bag, the furor began. Many daily newspapers and every major equine magazine published

articles on the condition. Unfortunately, the majority of the information was not only

embellished but also erroneous, causing a greater damaging effect on image of the American

Quarter Horse breed (Unknown 51). In order to stymie the speculation and erroneous

information being propagated regarding the disease, the AQHA, to their credit, began an effort to

educate people about the disease by publishing informative articles in the Quarter Horse Journal.

To this date AQHA continues to educate it’s members on HYPP and its effects.

WHAT ARE SODIUM ION CHANNELS?

Hyperkalemic periodic paralysis is the result of a gene mutation in the sodium ion

channel of the cell that occurred during the process of evolution. Most gene mutations of this

type do not propagate because the affected individual does not survive. For some unknown

reason Impressive survived and the mutation was passed on to some of his offspring (Unknown

52). To best understand the genetic defect you must understand what an ion channel is and how

it should work. The earliest understanding of how a cell membrane works can be credited to the
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work of Ernst Overton in 1899. He was able to demonstrate that certain types of tiny uncharged

dye molecules, which chemically resembled lipids, were able to make it into the cell easier than

other molecules that did not resemble lipids. Another scientist, Julius Bernstein, postulated the

Nernst equation, the ionic theory, and the assumption of a semi-permeable membrane and made

the first real theoretical contribution on cellular membranes (Unknown). In 1949 Hodgkin and

Katz were able to demonstrate a simple linear relationship between the level of sodium outside

the cell and the formation and amplitude of the action potential.

Figure 1. Na – K ATPase
(The Sodium-Potassium ATPase pump)
The Periodic Paralysis Association: An Online Biology Book
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Ion channels are specialized proteins that reside in the membrane and create aqueous pores

through which ions can travel. These ion flows across the cell membrane create an electrical

current that results in a change of the membrane potential. The membrane potential causes the

channels of the cell to gate (open and close). Ions responsible for the electrical excitability of

nerve and muscle include sodium (Na+), potassium (K+), and chloride (Ca2+) (Murrell-

Lagnado).

HOW DO ION CHANNELS WORK?

The operation of these ion channels is a highly controlled process. The type of channel

determines the type of stimuli (chemical, electrical, or mechanical) that it responds to (Murrell-

Lagnado). Voltage-activated channels are stimulated by a change in membrane potential while

those activated by an external chemical ligand (a molecule that binds to them) are called ligand-

activated. Voltage-gated ion channels are the ion channels found in nerve and muscle tissue and

the ones affected by the genetic mutation that causes HYPP. With the onset of cloning, well

over 100 ion channel genes have been cloned. With the predicted amino acid sequence it has

been demonstrated that there are families of related ion channels that must have evolved from the

same ancestral gene by the process of gene duplication and subsequent sequence divergence.

The ion channel structure found in a variety of life forms including plants, paramecia, bacteria,

and animals are all similar, demonstrating that these channels appeared very early in the

evolutionary process (Murrell-Lagnado). Molecular genetics has enabled us the ability to reveal

an increasing number of hereditary diseases that have been identified as being caused by

mutations in genes that encode ion channels; the most well-known one being cystic fibrosis.
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Others include hypo- and hyper-kalemic periodic paralysis and (para) myotonia congenital

(PMC), and potassium-aggravated myotonia (Leiden University Medical Center).

THE FUNCTION OF A MUTATED ION CHANNEL

This particular flaw affects the cell membrane by disrupting the normal opening and

closing of the sodium ion channel. These channels are "pores" in the muscle cell membrane,

which serve as gateways controlling the flow of sodium and potassium in and out of the cell.

This flow controls the muscle fiber contraction and relaxation. In an affected horse these

gateways malfunction and begin to leak, allowing potassium to flow out and sodium to flow in

(Spier, Klapheke, and Cahill 18). Ion channels are fairly sophisticated mechanisms. In normal

circumstances, at resting potential the activation gates to the voltage gated sodium ion channel

are closed. As the transmembrane potential approaches the threshold, the membrane becomes

more permeable to sodium as the sodium channels become activated. Sodium is driven into the

cell by the electrochemical gradient and the transmembrane approaches full depolarization,

which causes the inactivation gates of the channel to close. This in turn opens the voltage

regulated potassium ion channels resulting on the flow of potassium out of the cell decreasing

the transmembrane potential or repolarization. As the transmembrane potential returns to normal

resting levels, normal permeability is restored (Dehn).

THE GENETICS OF THE MUTATION

An autosomal dominant point mutation of the alpha subunit in the voltage gated sodium

ion channel SCN4A gene disrupts this process. The mutation expresses an impairment of rapid

inactivation and affects how the protein in the cell membrane operates by disrupting the voltage

gate resulting in the abnormal opening and closing of the sodium ion channel (Dehn). This
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disruption decreases the separation between a threshold and resting membrane potential resulting

in excitable membranes. Individuals with the disorder possess membrane potentials closer to

threshold resulting in muscle excitability. Healthy individuals have a membrane potential of

about –70 mV while affected individuals have membrane potentials around –55 mV.

The sodium ion ‘pump’, the process by which sodium and potassium flow in and out of

the cell, actively transports substances across a concentration gradient using adenosine

triphosphate (ATP). In a normal state sodium is at higher concentrations outside of the cell

while potassium is higher within the cell. Homeostasis is maintained by the flow of ions across

the concentration gradient, and thus a cell volume is maintained in a stable state. The muscle

fiber contraction and relaxation is controlled by this flow. In individuals affected by HYPP these

gateways malfunction and begin to leak, allowing potassium to trickle out and sodium to trickle

into the cell. The increased cellular level or sodium reduces the threshold membrane potential

resulting in bursts of persistent activity during which the normal opening and closing of the

channel is disrupted maintaining a state of depolarization (Unknown). This in turn causes the

potassium ion channel to continuously open resulting in the unregulated movement of potassium

out of the cell. These membranes are initially hyper excitable until extracellular potassium

accumulates to a point where gradual depolarization occurs and the cell eventually enters a state

of flaccid paralysis. The disease affects only skeletal muscle tissue as demonstrated by the

effect of the gene on sodium transport within skeletal muscle fibers.

The proper function of muscles and nerves is dependent upon potassium and every bodily

cell is comprised of potassium, which plays a vital part in preserving the "charge" in the

excitable muscle cells and nerves. Potassium “pools” in the body’s muscle and therefore skeletal
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muscle contains the highest levels of potassium. The concentration of potassium in the blood is

25 times lower than that in cells and is controlled by various hormones including insulin,

adrenaline, aldosterone, and thyroid. Studies found that affected individuals' muscle was

abnormal in the permeability of both sodium and potassium and that the muscle content of water

and sodium were higher and potassium lower than a normal individual. Individuals who

experience an attack have been found to have higher levels (.50 to 12.0 mEq/L) of potassium in

their blood than normal (3.0 to 4.5 mEq/L) (Spier and Carlson 68).

The equine disease has been determined to be analogous of the human version of the

disease (Rudolph, et. al. 248). Research on the human version identified two point mutations in

the cytoplasmic loop region of the SCN4A (neuronal sodium channel type 4) gene at the 17q23-

q25.3, near the growth hormone (GH) cluster. Notably, numerous elements of the GH1 gene

critical to tissue-specific transcriptional activation of the GH1 gene lie within the SCN4A gene.

The two mutations identified were in the III-IV cytoplasmic loop connecting transmembrane

domains III and IV. One mutation was a G-to-T transversion resulting in a substitution of valine

for a glycine that is one of a pair of glycines present in all known sodium channels. The second

was a C-to-T transition resulting in a thr-to-met substitution 6 amino acids beyond the location of

the site of the valine to glycine change observed in the first mutation. The disease in horses

presents itself as a phenylalanine-to-leucine mutation in transmembrane domain IVS-3 known to

disrupt fast channel gating (Fraser).

HEREDITARY TRAITS

HYPP is an autosomal dominant trait (heritable defect) meaning that it is not sex related.

Both males and females have an equal chance of inheriting the gene. Because it is a dominant
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gene it does not become “diluted” and is passed from one generation to the next on an equally

frequent basis (Unknown 52). The disease is not infectious or contagious - it is genetic in origin.

If a heterozygous individual (N/H), those having one copy of the gene, is bred to a

normal individual, fifty percent of the offspring will be normal (N/N) while the other fifty

percent heterozygous (N/H). If you were to breed two heterozygous individuals to each other,

fifty percent would be heterozygous (N/H), twenty-five percent normal (N/N) and twenty-five

percent homozygous (H/H), those carrying two sets of the gene. Less than 1% of the horses

tested were H/H, or homozygous for the gene.

Figure 2
Distribution of the HYPP

There is no set pattern for inheritance - it is strictly random in nature (Groves 53). By

breeding a genetically normal (N/N) individual to another genetically normal individual all

possibilities of producing an offspring affected with the mutation are removed. The disease is
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dominant not recessive therefore it does not skip a generation. At least one parent has to possess

the defective gene (heterozygous or homozygous) in order to pass it on to the offspring.

CLINICAL SYMPTOMS

Among heterozygotes a great deal of variation in the severity of symptoms exists. These

individuals presumably express both normal and mutated proteins from the corresponding

alleles. The concentration of mutant mRNA is related to the degree of gene expression and the

severity of disease symptoms (Dehn). HYPP attacks vary significantly in etiology, duration and

severity. Much of it depends upon the individual. Not every horse that tests positive for the

HYPP gene is symptomatic. Some horses possessing the HYPP gene go through their entire life

and never experience an attack. Heterozygous horses (N/H), are more likely to have mild or no

attacks at all. Homozygots (H/H), those horses having both copies of the gene, are more likely to

experience attacks with more frequency and of a higher severity (Groves 54), though this is not

scientifically proven. Usually, if a horse is going to experience and attack they will do so by the

time they are five years of age but keep in mind that any individual may experience an attack

regardless of age. Genetic predisposition, stresses, and diets all factor into the probability of a

horse having an attack. The least understood factor is genetic predisposition, which is the

inherited probability of having an attack. However, it has been determined that once an

individual has suffered an attack, it is highly likely that it will experience another (Gesel 16).

The key is in identifying the stressor, which initiated the attack in order to lower the chances or

prevent it from happening again.

Because the symptoms of an HYPP attack can mimic those of other equine disorders,

such as colic or “typing up” it can be very difficult to diagnose by simple observation. Some
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signs of an episode are periodic muscle spasms or tremors (which look like something crawling

under the skin), recumbency, dog sitting, sweating, prolapse of the third eyelid, and the inability

to rise for long periods of time. In the case of a homozygous individual, an attack can be

accompanied by noisy breathing caused by the paralysis of the throat muscle (Spier, Klapheke,

and Cahill 18-19). Some horses may loose complete muscle control and collapse. Death may

occur in rare cases but it is usually attributed to cardiac arrest and or respiratory failure

(Unknown 52). Horses who experience their first attack oftentimes appear confused and

frustrated with what is happening to them. Many individuals, who have experienced several

episodes, appear less confused, seem to know what to expect, and more generally are less

stressed or anxious with the situation.

TREATMENT FOR THE CONDITION

Treatment for mild attacks can be as simple as orally administering white corn syrup or

sodium bicarbonate. Both substances work to lower the serum potassium level and diminish the

attacks. Some horse owners top dress their horses daily ration with sodium bicarbonate as a

preventative. Though this is not a published curative, those who use it report good results. In

the event of a more severe attack a more aggressive approach may be required. Treatment in this

case can include, but is not limited to, administering medications intravenously. These

medications can include calcium gluconate 23%, sodium bicarbonate 5%, Dextrose 5%,

furosemide 50 mg/ml, and epinephrine (1:1000). Each of these treatments will help to lower the

potassium level in the blood and also help to stabilize the muscle membranes. To assist in the

animals comfort during a more sever episode, or to keep a minor episode from escalating, the

horse may be administered Banamine (a painkiller), a muscle relaxer, or an antispasmodic.

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WHAT ARE THE TRIGGERS OF AN EPISODE?

It is hard to factor stress into the likelihood of a horse having an attack since the types

and levels stresses differ greatly. For example, in a situation where two individuals are subjected

to the same living conditions and same types and levels of stresses - one might suffer an attack

while the other is unaffected. Trailering might cause and episode in one individual while

training or even foaling might trigger an attack in another. Hot, humid weather over long periods

of three or more continuous days seems to stress some HYPP horses and can initiate an attack. If

horses are stalled provide plenty of ventilation and a fan for cooling purposes. If housed outside,

be sure the horse has ample access to shaded areas. Always have plenty of water available for

these horses. Horses are creatures of habit and like consistent routines. Every effort should be

made to establish a routine for feeding and training. Try to avoid any sudden changes in routine

as it could cause stress. If changes need to be made they should be done slowly over a period of

time (Gesel 16-17).

DIET AND MAINTENANCE OF AFFECTED HORSES

A horses physiology depends a lot upon his diet therefore, diet is very important when

dealing with HYPP situations. You should avoid diets high is potassium levels (Gesel 17).

Since potassium seems to be the main factor triggering an attack, by lowering the amount of

potassium in the diet, the frequency of attacks can be diminished or eliminated. Most hays and

sweet feeds, which contain molasses, are high in potassium content. Some individuals may need

to be placed on a “complete” feed, that contains the hay and grain rations combined in a pelleted

form, which in turn allows for better control of potassium levels. Other horses can still be fed

hay while getting their grain source from high carbohydrate feeds such as oats, corn and barley.
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Still, others can be maintained on sweet feeds and hay without experiencing an episode (Spier,

Klopheke and Cahill 19-20). In most instances HYPP positive horses do well on diets of oats

and high quality hay. Contrary to much published information, alfalfa is a good choice of forage

especially for show horses and those in training. While it has a higher potassium level than

pangolagrass, ryegrass or oat hay, it is still lower in potassium than readily available hays such as

coastal bermudagrass, red clover, timothy and orchardgrass.

The 'total' dietary potassium level needs to be 1% of the total amount fed by weight. This

is tricky and necessitates an understanding of the levels of potassium in common feeds. Dry

grains such as corn, barley and oats are about 1/2%, and most alfalfa hay is 1.5%. Thus, if you

feed equal weighted amounts, you would be at the ideal 1% level of potassium. Beet pulp is high

in fiber and calories and low in potassium (.3%). This is optimal for HYPP horses though should

be supplemented with soy meal, which is higher in phosphorus, for younger horses to balance the

high calcium levels in alfalfa and beet pulp. Besides diet and stress management, exercise plays

a major role in maintaining the HYPP horse. Those affected with the HYPP gene do better with

daily turnout as opposed to stall confinement. Horses experiencing an attack will benefit from

light exercise such as walking or jogging, which increases the adrenaline thus lowering the

amount of potassium in the blood and stabilizing the episode. As stated previously, it is thought

that stress, especially in young horses, can trigger an attack (Spier, Klopheke, and Cahill 19-20).

Medication plays and integral part in HYPP maintenance for some horses, especially those who

suffer frequent or severe attacks. Acetazolamide is a mild diuretic that helps the liver and

kidneys shed the excess potassium however it takes approximately 12 hours after being

administered to become effective. Acetazolamide is now approved as a maintenance drug by the

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AQHA and can be used during competition however, it is still listed as a substance banned by the

ASHA during competition.

MEDICAL CONSIDERATIONS

It is very important to relate the HYPP status of an individual to your veterinary before

any surgical procedures so that the veterinary may monitor for any signs of attack during

treatment. Some tranquilizers, such as acepromazine, or those derived from phenothiazine

should be avoided because they can trigger an HYPP episode by increasing the serum potassium

level. Those tranqilizers acceptable for use in the HYPP positive horse include Rompun,

Torbugesic, and Dormosadan. Knowing the HYPP status of a patient also allows the vet to be

prepared in the event that a treatment regime creates a stressful situation for the horse and

induces an episode.

In humans, three variations of the mutation affecting the SCN4A gene have been

recognized (Fraser). A clinically similar but genetically different form of HYPP has also been

discovered in humans opening up the possibility that the same exists in horses. That possibility

is very intriguing to the scientific mind though most horse owners, especially those who have

been in the thick of the HYPP controversy, would not welcome that postulation.

It has been suggested that the mutation reflects the adverse effect of inbreeding in

thoroughbred where only 4 founding stallions are responsible for 30% of the gene pool

(Winand). If this is so then why did the mutation occur when the thoroughbred blood was

crossed with that of a quarter horse? Or did it? Is it possible that this disease, at least in some

form, exists in thoroughbreds? The thought is that there is generally some form of parental

consanguinity with the affected horses, that is, the parents are often related. Whatever the theory
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as to why the mutation occurred is, there is no question as to why it continued to propagate.

Impressive was a popular stallion whose phenotype, due to the expression of the effects of the

mutation (muscular stature), was highly sought and it was several generations before anyone

identified a problem. Even today those who possess the desired phenotype are highly sought in

breeding programs. Little or no thought is given by some as to the HYPP status of the animals to

be bred. What seems to be the most important to them is breeding the ability to win. Others

make a concerted effort to breed their affected animals to the best available non-affected

individual in an effort to produce a quality offspring that is, at the most heterozygous but

preferably unaffected. It is encouraging to note that, according to The Quarter Horse Journal

(2005), the top two stallions on the AQHA leading sires list are both N/N (Mr Yella Fella and

Touchdown Kid) and of the top twenty stallions three more are N/N (Perpetualism, Statutory,

and Coolest) (p. 158).

IN CONCLUSION

How many more genetic anomalies will be discovered only after several generations have

been produced? At least two are currently being researched. The first, Glycogen Branching

Enzyme Deficiency (GBED) results in the inability of the individual to process and store

glycogen resulting in death, often within several hours of birth. The second, Hyperlastosis Cutis

(HC) results in fragile skin, which can stretch excessively, tear easily, slough off and heals

slowly. While some affected individuals can live many years, most are euthanized. Both

mutations are autosomal recessively inherited genes and the effects of the defect are only

expressed in homozygotes. Both are also genetic defects recognized in humans. They are both,

for the most part, deleterious to the affected individual. The risk of producing an individual that
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is homozygous for a recessive allele can be calculated by methods such as percentage of blood or

the coefficient of inbreeding and is directly proportional to how closely the sire and dam are

related. As in HYPP, both sexes are affected equally as frequent and both sexes can pass on the

trait.

As we can see, many genetic mutations in horses correlate to the same mutation in

humans. With that in mind we can assume that it is only a matter of time before other mutations

indicative of the human genome are identified in the equine genome. It also makes it evident

that we have little or no control on when, where, and if these mutations occur. All we can do is

act as quickly as possible to identify them and make responsible breeding choices based on the

information at hand. The AQHA continues to fund research on HYPP and, since initial reports

were made, Dr. Sharon Spier, one of the preeminent authorities on the disease, issued the

following statement trying to bring the condition into perspective. "Horses afflicted with HYPP,

if properly managed, can lead productive, useful lives, and bring their owners many hours of

pleasure" (Unknown 51). Anyone who owns a horse with Impressive in its bloodlines should

have the horse tested if they suspect that the horse has had an attack. A DNA test developed by

UC, Davis in 1992 is currently the only way to confirm the presence of the HYPP gene in an

individual. The test can be performed from either a blood sample or with a strand of hair from

the suspected animal. Also, owners of HYPP positive horses should do their utmost to become

educated about the disease to better understand it, how to maintain their horse’s health, and how

to treat an episode.

Research on the equine form of the sodium ion channel mutation and HYPP has appeared

to come to a standstill. No new information or research has been forthcoming on the disease in
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almost ten years. Perhaps the funding sources went dry or a lack of interested researchers to

pursue additional avenues of the mutation and its expressions has occurred. Whatever the reason

the scientific community has left the horse owners hanging where this disease is concerned.

There are many aspects of this mutation that are left to wonder such as; is the mutation expressed

differently in different family lines? Are some family lines more prone to experiencing attacks,

or passing on the mutation? Is the mutation further evolving? Is the horses’ physiology adapting

to the mutation by creating working coping mechanisms to the effects of the mutation?

Amazingly, with the discovery of GBED and HC the furor over HYPP has died down

considerably. Perhaps people have had a reality check in the realization that animals are not

limited in the number of mutations that can occur. Like humans, their genetic makeup can

experience errors during any stage of the “manufacturing” process. One transposition, deletion,

or substitution can lead to a change in their genetics that will have no affect, a minor affect, a

major effect, and in some cases a deadly effect on the individual and/or their offspring. As can

be demonstrated, many genetic mutations in horses correlate to the same mutation in humans.

With that in mind we can assume that it is only a matter of time before other mutations indicative

of the human genome are identified in the equine genome. It also makes it evident that we have

little or no control on when, where, and if these mutations occur. All we can do is act as quickly

as possible to identify them and make responsible breeding choices based on the information at

hand.

STEPS TOWARD PROGRESS

The American Quarter Horse Association has taken initiative in addressing this particular

genetic disease. At the AQHA Convention in March 2004, the Stud Book and Registration
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Committee voted to require that all foals born in 2007 and beyond with bloodlines that trace to

Impressive be parentage verified and a tested for HYPP following AQHA rule 205 (c)(1). Any

foal born in 2007 or thereafter that tests homozygous positive (H/H) for HYPP will not be

eligible for registration with AQHA. While this measure removes any incentive for breeding

heterozygous individuals to heterozygous individuals, it will not eliminate it. Many of the top

stallions are heterozygous and those people with heterozygous mares are still going to seek out

the best stallion to breed their mares to, taking the risk of an unregisterable foal. With many of

the top stallions now offering an HYPP guarantee, mare owners will have a chance to rebreed

when a homozygous foal is produced from the cross. That removes much of the financial risk

they take when making their breeding decision.

What happens then to all of those homozygous unregistered foals? Unfortunately they

will most likely be dumped at local auctions as grade horses where unsuspecting buyers with

little or no knowledge of the condition will become the owners of medically challenged horses.

The decision to not register homozygous individuals needs to be rethought. By maintaining

registration records on these individuals more accurate records can be maintained by the

registering organization on exactly how many affected horses are being produced each year. It

also enables accountability for education and proper care of affected individuals. Perhaps

incentives can be offered to those owners demonstrating responsible breeding practices and who

make an effort to produce genetically normal (N/N) individuals.

It has been suggested that affected individuals should be removed from breeding. This

also is not a viable option. Not only would it result in insurmountable financial losses to those in

the business of breeding quarter horses but it would also limited the viable equine gene pool. By
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limiting the available gene pool a larger quantity of horses would be crossed on individuals with

similar genetic make-up presenting a pathway for further genetic mutations to develop. A

program of out crossing to add hybrid vigor should be encouraged. It is also imperative that

other breed organizations, such as APHA, ApHC, PHBA, and PtHA, who allow crosses with

AQHA horses into their registration follow AQHA’s lead in addressing HYPP and other

identified genetic diseases. This is the only way to decrease the incidence of this and other

genetic diseases within the equine populations.

 Hyperkalemic Periodic Paralysis Page 23

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