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HYPP - Unmasking the Fatal
Flaw
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Portions of this article are written based
on the article "Unmasking the Fatal Flaw" by Jack Moore along with
information published online from the UC Davis School of Veterinary
Medicine. |
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Impressive Syndrome
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More than 30 years have passed since the yearling Quarter
Horse stud colt Impressive was purchased for $20,000 at the Indiana State
Fair. In three months time, his owners doubled their investment, selling
Impressive for $40,000 and feeling that they had turned a tidy profit. |
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Little did anyone know at the time that they had in their possession the
horse which would prove to be one of the top-winning, top-producing Quarter
Horse stallions of all time. It soon became evident that Impressive would
live up to his name, winning 31 blue ribbons out of 31 attempts in the
halter ring. As a breeding stallion, he proved himself equally deserving of
his name, turning out champion after champion. Many of Impressive's
offspring bore the same dramatic physical stature as their sire - they, too,
went on to become outstanding and prolific stallions and broodmares.
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Of the top 15 halter horses in 1992, 13 were descendants of Impressive.
Even at the age of 23, Impressive himself was fourth on the list. In 1993,
it was estimated that more than 55,000 Quarter Horses, Paints, and
Appaloosas world-wide bore his pedigree. Today that number is in the
hundreds of thousands. |
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But what seemed like a winning streak to go down in history was soon to be
overshadowed by tragedy. Greatness, unfortunately, was not the only thing
that Impressive passed on. He has also been linked to a genetic mutation
that has been implicated in the rare but burgeoning - and
sometimes fatal - muscular disorder known as hyperkalemic periodic
paralysis. This particular defect is a dominant condition, meaning that at
least half of the affected horses' offspring will be affected as well. In
the words of one prominent Quarter Horse trainer, this discovery was "one of
the most devastating things that has ever hit the horse industry."
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Within a few years of Impressive's ascendancy to the top of the sire's list,
halter horse owners began to notice a strange muscular twitching that often
left their horses temporarily unable to move. Usually mis-diagnosed as
tying-up syndrome or colic, these episodes varied widely in degree and
duration....but all had one factor in common, their pedigree. As a
result, many people now know HYPP as its more common name: Impressive
Syndrome |
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Research funded by the AQHA and the
University of California-Davis Equine Research Laboratory subsequently
linked the problem to elevated levels of potassium in the blood serum.
But even as researchers at leading veterinary schools began publishing
articles in professional journals and trade publications, the vast
majority of Quarter Horse owners remained unaware of the condition |
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All the while, Impressive and his kin continued to make
history.....breeding, showing, winning ribbons, and making their owners
fantastic sums of money. Most affected horses can be controlled quite well
with medication and a proper low-potassium diet, therefore, many owners of
affected horses considered HYPP a minor inconvenience in light of the line's
tremendous value. Given the fact that - at the time - there was no proof
that the disorder was exclusive to the Impressive line - not to mention the
fact that owners of stock descended from Impressive included some of the
most prominent and wealthy individuals in the industry - no one wanted to be
the first to publicly implicate the line. And, even later, when a
breakthrough genetic test removed all doubt, lessening the moral and ethical
burdens associated with naming Impressive as the carrier, neither the
research community nor the AQHA was eager to lift the lid of this Pandora's
box: Each feared possible legal and financial ramifications from a sector of
the horse industry that would be shaken to its foundations. |
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In the past few years however, pressures
both within and outside the Quarter Horse industry finally shattered the
secrecy surrounding HYPP. The genetic test, made available in 1992, can
identify affected horses with virtual certainty. As a result, many
owners of horses descended from Impressive have rushed to have their
horses tested, hoping that a negative result would protect their
considerable investment against the anticipated backlash. Breeders have
purchased advertising in The Quarter Horse Journal touting their
HYPP-negative test results, and privately have urged their peers to
either test their Impressive bred horses, or remove them from breeding. |
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From the Vet School at UC
Davis, California
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Blood Test Available for Hyperkalemic Periodic Paralysis
in Quarter Horses By Sharon J. Spier, D.V.M., Ph.D. University of California
at Davis School of Veterinary Medicine, Department of Medicine. |
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Hyperkalemic periodic paralysis (HYPP) is a muscle disease
which has been reported in certain lines of registered Quarter Horses,
Appaloosas and Paints. Affected horses often display well-developed muscles
and are often very successful when shown in halter classes. The condition
may be seen in stallions, mares or geldings, can cross breeds and,
therefore, is not limited to stock-type horses. The disease also closely
resembles a heritable disease in man. Studies at the University of
California at Davis Equine Research Laboratory have produced much needed
information about the genetics, cause and control of HYPP in horses. An
accurate blood test has been designed for diagnostic purposes as well as to
identify carriers of the disease. |
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Signs of the Disease |
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Hyperkalemic periodic paralysis is characterized 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. |
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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 this disease from "tying-up" syndrome
though, 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. |
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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, however, 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.
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Causes of Attacks |
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Potassium is an important electrolyte and is vital for the
normal function of muscles and nerves. In fact, every cell in the body
contains potassium, as it is vital for maintaining the cell's volume and
electrical activity. High concentrations of potassium are present in the
normal diet of horses and large amounts are found in forages such as pasture
grasses and hays. |
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Regulation of body potassium is very complicated and is
strictly controlled by hormones throughout the body produced by the kidneys,
adrenal gland, thyroid and pancreas. Because normal horses commonly consume
an excess of potassium in their diets, the kidneys must excrete excess
potassium in urine. Initially, it could not be determined whether this
disease was caused by a disorder in potassium regulation or by a disorder of
muscle function. Studies of kidney, adrenal gland and thyroid function in
horses with HYPP were normal. Investigations of muscle function in these
horses, however, revealed a different story. |
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In early studies, abnormalities in the skeletal muscle by
electromyography (EMG) were observed. Electromyography measures the
electrical activity present in selected muscles. In affected horses, the
muscles displayed a wide variety of abnormalities, specifically spontaneous
activity from muscles under no stimulation. These recordings demonstrated
that the affected horses' muscles were hyper-excitable (overly excitable).
Even when the horses appeared normal, in between attacks, the abnormalities
were reproducible. These abnormalities were also observed when the horses
were under general anesthesia and under the influence of nerve blocking
agents. This proved the theory that the muscle was abnormal. |
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Abnormal electrical activity within muscle fibers occurs
in other muscle diseases as well as HYPP, so the abnormal EMG findings are
not enough to definitively diagnose HYPP. Nonetheless, repeated episodes of
muscle weakness or tremors in offspring of an affected sire or dam coupled
with abnormal EMG findings would be highly suggestive of HYPP. |
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Collaborative studies with human physiologists Drs. Joel
Pickar and Richard Carlsen of the University of California Davis School of
Medicine and Dr. Jack Snyder of the veterinary department of Surgery led to
the development of a specialized muscle biopsy procedure for horses which
allowed researchers to isolate and study small muscle strips in a laboratory
setting rather than performing research on the whole horse. Results from
these studies confirmed that the isolated muscle was hyper-excitable and that
there were abnormalities in sodium and potassium levels. |
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In horses with HYPP, studies revealed a defect affecting a
protein called the voltage-gaited sodium channel, a tiny gateway in the
membrane of muscle cells. This gateway controls the movement of sodium
particles in and out of the muscle cell. These sodium particles carry a
charge that changes the voltage current of a muscle cell, allowing it to
contract or relax. In horses with HYPP, the regulation of particles through
the sodium channel occasionally fails, disrupting the normal flow of ions in
and out of the muscle cell, causing uncontrollable muscle twitching or
complete muscle failure. |
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Further studies using molecular genetics revealed a
mutation at one important site in the gene responsible for sodium and
potassium regulation. This mutation allows the production of an abnormal
protein which alters the structure and function of the sodium channel. As a
result of these uncontrollable muscle contractions, potassium leaks from
inside the muscle cell into the bloodstream, thus, raising the blood
potassium concentration. The identification of this gene mutation is the
basis for the blood test used to diagnose HYPP. |
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An Inherited Trait in Horses: Breeding Trial Results |
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In humans, HYPP is inherited as a dominant trait which is
not sex-linked or carried on the X or Y chromosomes, and either sex may
carry the trait. The proportion of individuals carrying a genetic defect
which actually demonstrate signs of the disease is called penetrance.
Sometimes, an individual can carry a genetic defect, but may never show
signs of disease. In humans, HYPP has a high penetrance, meaning that the
majority of individuals carrying the gene will demonstrate signs of disease
at some time during their lives. |
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The mode of inheritance of the disease in horses has been
suggested to be similar, although there had been no definitive studies to
prove this theory. The purpose of the breeding study was to document, in a
laboratory setting, the mode of inheritance of HYPP in horses through a
controlled breeding study. |
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Four Quarter Horses (one stallion and three mares) with
HYPP were bred to unaffected horses to determine the genetic basis of the
disease. The first trial consisted of breeding the affected stallion to an
affected mare. Three offspring (two colts and one filly) were obtained using
embryo transfer techniques and all three foals were affected with HYPP. This
initial study proved that the condition was heritable, but could not
distinguish if the trait was dominant or recessive. |
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The second trial consisted of breeding the affected
stallion to 11 unaffected mares of different breeds. The three affected
mares were bred to an unaffected Quarter Horse stallion. Seventeen foals
were produced from these breedings. All foals were tested for HYPP at two
months of age. Of the 17 offspring, 10 were affected with HYPP, proving that
HYPP is a dominant trait. |
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Because HYPP is a dominant trait, the breeding of an
affected mare or stallion to a normal horse will result in approximately 50%
of the offspring carrying the trait. If two affected horses are bred, then
at least 75% of the foals will be affected. The breeding of a normal
offspring from an affected horse to another normal horse will result in
normal offspring. |
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Prevention and Control of HYPP Attacks |
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During a severe attack of HYPP, emergency treatment from a
veterinarian is necessary. For long term therapy, many horses can be managed
by exercise and diet control alone. Regular exercise and access to a large
paddock or pasture is preferred over stall confinement. Maintain a regular
feeding schedule, preferably equally spaced, two to three times per day.
Avoid rapid changes in feed, such as bringing a horse off pasture grass and
immediately switching to alfalfa hay. Most horses improve when the potassium
content in the diet is decreased. |
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An analysis of feed can be very helpful in problem
situations. Oat hay contains approximately 1.4% potassium, alfalfa hay -
approximately 2.5%, timothy hay - approximately 2.0 - 2.5% potassium and
molasses - approximately 6% potassium. The HYPP horses at the Equine
Research Laboratory do well on a diet of half alfalfa and half oat hay.
Feeding grain such as oats, corn and or barley (each contain only 0.5%
potassium) two to three times daily and access to a salt block can be
helpful. If dietary management is not sufficient to prevent attacks, then
treatment with a diuretic (acetazolamide) can be very helpful. Consult your
local veterinarian for proper diagnosis and further recommendations on
treatment. |
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Eliminating this Disease from the Horse Industry |
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The major focus of this study has been to develop the use
of a genetic marker associated with HYPP to identify affected horses to
assist veterinarians and breeders in controlling the disease. In
collaboration with Dr. Eric Hoffman, a molecular geneticist from the
University of Pittsburgh School of Medicine, a horse-specific HYPP gene
probe was created using DNA from the affected Quarter Horse stallion. This
gene probe offers breeders and veterinarians a tool which can be applied as
a safer and more reliable diagnostic test for this disease. |
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Affected horses which are carriers of this genetically
determined disease have many desirable traits. This is the reason that many
of these horses are so successful in the show ring. In a recent report by
Dr. Jonathan Naylor of the University of Saskatchewan, over 50,000
registered Quarter Horses are related to known carriers of the disease.
However, the disease is not widespread in the Quarter Horse breed and only
involves certain lines of halter type horses. At the present time, the
disease has not been recognized in racehorses or endurance horses.
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The recently developed genetic marker test for this
disease will allow breeders to identify carriers of HYPP and thus,
direct their breeding programs. To eliminate this trait from certain
lines, stallion and mare owners should have their horses tested prior to
breeding and select normal horses for their breeding stock. |
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Myths About HYPP |
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Some people have felt 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. Some people also believe 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 realize 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 that owners
have discovered the best management strategies for the older horses with
HYPP. |
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Some people also think that 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. |
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Owners and breeders of affected horses should inform
prospective buyers of the management constraints these horses have and the
potential for future episodes of HYPP. To have a horse tested for the
specific DNA mutation causing HYPP, contact the Aerican Quarter Horse
Association at www.AQHA.com and
download the correct forms. |
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Special Note:
The American Quarter Horse Association has revised the
rules of "Impressive" descendants whereas: |
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Rule 205(c)(3) states: |
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"Effective with foals born on
or after January 1, 2007, all descendants of the stallion Impressive,
AQHA registration No. 0767246, shall be required to be parentage
verified and HYPP tested, subject to the conditions in Rule 205(c)(2).
Any foal testing homozygous for HYPP (H/H) will not be eligible for
registration with AQHA." |
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There is a misconception in
some circles that (H/N) or (N/N) tested horses are not carriers of HYPP.
This, of course, begs the question: Why does the AQHA require
testing? |
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The truth is...geneticists
don't know for sure. AQHA's only answer is to keep testing because
no one knows what will trigger the mutation. |
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The correct remedy is at every
breeder's disposal...Don't breed to Impressive
horses. They have a genetic defect
within their DNA structure, and, anyone that tells you differently is
simply not telling the truth. |
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The reality is that there is a
multitude of exceptional Quarter Horses in the world that can be bred
to. Why perpetuate the problem, or take the chance with your foal?
Simply... it's irresponsible. |
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