HYPERKALEMIC PERIODIC PARALYSIS

A Comprehensive Brochure to Inform & Educate American Quarter Horse Enthusiasts

Dear American Quarter Horse Enthusiast,

For some time now, you have probably heard, or had first-hand knowledge, of the condition known as hyperkalemicperiodic paralysis (HYPP). This condition is characterized byintermittent episodes of muscle tremors (shaking or trembling,weaknesses and /or collapse).

At the 1996 AQHA Convention in Seattle, Washing-ton, the AQHA Board of Directors approved some ruleswhich will have substantial effects on the future of the registry. These rule changes wererecommended by the AQHA Stud Book and Registration Committee and approved bythe Board of Directors. Among the changes was a rule requiring disclosure of HYPP sta-tus on the registration certificates of foals born on or after January 1, 1998, whichdescend from any bloodline determined to carry the HYPP gene.

Beginning with the 1997 AQHA Official Handbook, HYPP will be listed in rule 205among conditions commonly considered undesirable traits or genetic defects, such asparrot mouth and cryptorchidism. These conditions do not prevent a horse from beingused as breeding stock or from participating in AQHA-approved events, subject to rulesof the individual event.

Beginning with 1998 foals, the rule requires the following notification to be placedon the registration certificates of foals descending from any bloodline determined tocarry the HYPP gene:

“This horse has an ancestor known to carry HYPP, designated under AQHArules as a genetic defect. AQHA recommends testing to confirm presence orabsence of this gene.”

Facts about HYPP have been gained through research projects funded in part byAQHA, through the University of California, Davis and the University of Pennsylva-nia. The first report, from Drs. Sharon Spier and Gary Carlson of U.C. Davis, was deliv-ered to AQHA in the summer of 1992, and published in-full in the September 1992issue of The Quarter Horse Journal. As additional information has been made available,AQHA has promptly published it. I invite you to refer to the last page of this brochurefor a list of AQHA publications and others which contain information about HYPP.

AQHA has a duty to its members and American Quarter Horse owners to keepthem abreast of current information on HYPP, and indeed, all health matters, so thatthey may make informed decisions concerning their equine programs. In furtherance ofthese objectives, AQHA has published this brochure, “HYPP: A ComprehensiveBrochure to Inform & Educate American Quarter Horse Enthusiasts.”

Respectfully,

Bill BrewerAQHA Executive Vice President

Hyperkalemic Periodic ParalysisFACT SHEET

Prepared by the American Quarter Horse Association, September 1996

From AQHA’s Official Handbook of Rules and Regulations

RULE 205: GENETIC DEFECTS and UNDESIRABLE TRAITSThe conditions listed below and commonly considered unde-

sirable traits or genetic defects by the Board of Directors shall beindicated on the registration certificate for horses foaled on orafter the indicated date, once the condition is known. Upondiscovery, the owner shall immediately report such conditionto AQHA for marking its condition on the registration cer-tificate as provided below. Failure to timely report these con-ditions may subject the owner to possible disciplinary action.One or more of these conditions does not prevent a horse frombeing used as breeding stock or from participating in AQHA-approved events, subject to rules of the individual event:

[a] Parrot Mouth - either overshot or undershot, defined by theAmerican Association of Equine Practitioners as “no occlusalcontact between the upper and lower central incisors.” Desig-nation effective for foals born on or after January 1, 1992.

[b] Cryptorchid - meaning less than two visible testicles descendedinto the scrotum. Designation effective for foals born on or afterJanuary 1, 1992.

[c] Hyperkalemic Periodic Paralysis (HYPP) - designation effec-tive for foals born on or after January 1, 1998. A muscular dis-ease caused by a hereditary genetic defect that leads touncontrolled muscle twitching or profound muscle weakness,and in severe cases, may lead to collapse and/or death. Accord-ing to research, this condition exists in certain descendants ofthe the stallion Impressive, AQHA registration number0767246.

[1]The following notification shall be placed on registrationcertificates of foals descending from the stallion Impres-sive or any other bloodline determined to carry the HYPPgene:“This horse has an ancestor known to carry HYPP, designatedunder AQHA rules as a genetic defect. AQHA recommends test-ing to confirm presence or absence of this gene.”

When the parent(s) tracing from the HYPP line has test-ed negative for HYPP with an appropriate designationappearing on their registration certificate, the above notifi-cation is not required, and will, instead, be substituted bythe designation “N/N”; or, after testing negative for thegene, the notification may be substituted by the designation“N/N” upon request of the owner at his or her expense.

[2] Mandatory testing for HYPP. At such time as AQHArequires mandatory parentage verification of any foals tobe registered in either the numbered or appendix registry,(see 202 (i)) any foal tracing to bloodlines known to carrythe HYPP gene shall be tested for HYPP at the time thegenetic testing for parentage is performed. The results willbe designated on the registration certificate in lieu of theabove notification. Such testing will not be necessary ifthe foal’s closest ancestors, tracing to the HYPP line, havebeen tested negative and designated on their registrationcertificates, these foals will automatically be designated“N/N” on their registration certificate.

Hyperkalemic periodic paralysis (HYPP) is an inher-ited disease that leads to uncontrolled muscle twitch-ing or profound muscle weakness, and in severecases, may lead to collapse and/or death.

HYPP is listed as a genetic defect in AQHA’s rules,along with Parrot Mouth and Cryptorchid conditions.

To date, HYPP only has been traced to descendantsof IMPRESSIVE, #0767246.

Having negative (N/N) results on file may prevent ahorse’s offspring from being tested.

Foals born in 1998 and later and tracing toIMPRESSIVE will have a statement placed on theirCertificates of Registration that recommends testingfor the condition unless test results indicating thefoal is negative (N/N) are on file with AQHA.

AQHA will test any foals who are required to beparentage verified and who trace to IMPRESSIVEfor HYPP prior to them being registered. This testingwill be performed with the same DNA sample sub-mitted to the laboratory for parentage verification.

AQHA will accept HYPP test results only if performedthrough a licensed laboratory.

Beginning with the 2007 foals, all Impressive progeny arerequired to be parentage verified and HYPP tested subjectto the conditions listed in rule 205. Any that test H/H willnot be eligible for registration.

Possible results of HYPP testing are N/N, N/H and H/H.

HYPP is inherited as a dominant trait, which meansa heterozygous (N/H) stallion or mare bred to a nor-mal (N/N) horse will result in approximately half ofthe offspring being affected and half being normal.The rare homozygote (H/H) usually is severelyaffected with the disease and will pass the gene to itsoffspring 100 percent of the time.

HYPP can be treated through diet and medication inmost cases.

AQHA Testing Kits can be ordered for $35. (seeback cover)

his report will update AQHA mem-bers on research that has been per-formed since DNA testing becamewidely used in the horse industry.Studies were performed to try toanswer specific questions regardingthis genetic disease. just how wide-

spread the mutation was in the Quarter Horsebreed and where the mutation originated wereunknown. While the gene frequency in QuarterHorses was not known, at the time of identifica-tion of the genetic mutation, all affected horsestraced to a common sire.

The reason(s) for the variation of clinicalseverity of symptoms, ranging from no apparentsigns of disease to sudden death, were unclearand warranted investigation. There was alsoconcern among horse owners about the possibil-ity of episodes of paralysis occurring during exer-cise when an affected horse is ridden. A series ofexercise studies were performed in effort to try toanswer some of these questions.

Hyperkalemic periodic paralysis (HYPP) is aninherited disease of muscle which is caused by agenetic defect in the alpha-subunit of the adultmuscle sodium channel gene. The disease isinherited as an autosomal dominant trait, whichmeans that only one copy of the gene is requiredto produce the disease, and the disease occurswith equal frequency in both sexes (stallions,geldings or mares). The disease is strictly genetic(i.e., not infectious or contagious) and breedingof a heterozygote results in approximately 50percent of the offspring that will not possess themutation (normal) and 50 percent of the off-spring that will possess the mutation (affected,heterozygote). The transmission is purely ran-dom, that is, much like flipping a coin.

Presence of the defective sodium channelmakes the horse’s muscle overly excitable (firingmore readily than normal), making the horsesusceptible to sporadic episodes of muscletremors or paralysis that can last from minutes tohours. The majority of the time, affected horsesappear clinically normal and many are highlysuccessful show horses (both halter and plea-sure), while others are used for pleasure and trailriding. The mutation can be identified from aDNA test and is available through the Veteri-nary Genetics Laboratory at the University ofCalifornia at Davis.

HYPP gene frequency studyMore than 27,000 samples have been tested forthe DNA mutation since October 1992. Ofthese, 63 percent were normal (N/N), 36 per-cent were heterozygous for HYPP (N/H) and 1percent were homozygous affected (H/H).

For AQHA to provide satisfactory answers toquestions about the frequency of the HYPPmutant gene among Quarter Horses, a randomtesting program not skewed to a single bloodlineis needed. Responsible owners frequently ask foradvice whether to incur the expense of testinghorses that do not trace to Impressive, but dotrace to his Thoroughbred or Quarter Horse par-ents or grandparents. At the time of the pro-posed study, we did not have adequate answersfor these inquiries. Data summaries from anHYPP service testing program cannot providethe needed information since the samples testedare likely to be either from horses showing pre-sumptive signs of the disease or from horseswhose pedigrees trace to Impressive.

What is HYPP?Hyperkalemic Periodic Paralysis (HYPP) is a muscu-lar disease that affects both horses and humans. It iscaused by a hereditary genetic defect that disrupts aprotein called a sodium ion channel, a tiny gatewayin the membrane of muscle cells. The genetic defectdisrupts the channel’s normal opening and closing,such that uncontrolled sodium influxes occur. Theseinfluxes in turn change the voltage current of musclecells, causing uncontrolled muscle twitching or pro-found muscle weakness. High levels of potassium inthe blood usually are present when the disruptions inthe ion channel occur.

What are the effects of HYPP?Horses with HYPP can experience unpredictableattacks of paralysis which, in severe cases, can leadto collapse and sudden death. The cause of deathusually is cardiac arrest and/or respiratory failure.The disease is characterized by intermittentepisodes of muscle tremors manifested by general-ized or localized shaking, trembling and weakness.Occasionally, episodes are accompanied by respira-tory noises resulting from paralysis of the musclesof the upper airway (larynx and pharynx). In casesof mild attacks, muscle tremors may be so subtle asto be detectable only by an experienced clinicianperforming EMG testing.

Can symptoms of HYPP varyin severity?Clinical signs of HYPP do vary widely among differ-ent horses. Homozygous horses are affected moreseverely than heterozygous horses. Under idealmanagement practices, the defective gene does notappear to have adverse effects, but stress and/orincreased potassium in the serum can trigger clinicalsigns of muscle dysfunction. Why some horses man-ifest severe signs of the disease and others exhibitlittle or no signs is unknown, but currently underinvestigation. Unfortunately, a horse carrying thedefective gene, but showing minimal signs, has thesame chance of passing the gene to future genera-tions as does the affected horse with severe signs.

What is the origin of thegenetic defect causing HYPP?The original genetic defect causing HYPP was a nat-ural mutation that occurred as part of the evolution-ary process. The majority of such mutations, whichare constantly occurring, are not compatible withsurvival. However, the genetic mutation causing

HYPP produced a functional, yet altered, sodiumion channel. This gene mutation is not a product ofinbreeding. The gene mutation causing HYPPinadvertently became widespread when breederssought to produce horses with heavy musculature.

Is HYPP limited to a particularbloodline of horses?HYPP is associated with horses of heavy muscula-ture, but this does not mean that all horses withwell-developed musculature are affiliated with thedisease. The mutant gene causing HYPP presentlyhas been identified in the descendants of the horseImpressive. Research has not yet been performedon other bloodlines to ascertain whether the sameor similar genetic mutation existing in otherbloodlines also may cause HYPP. Since Impressivedescendants are so numerous, the genetic mutationin this bloodline is widespread. Theoretically, it ispossible that other mutations causing HYPP in dif-ferent bloodlines may be more difficult to identifybecause they are not so wide-spread.

HYPP is unique in that it is the first equinedisease in which breeding and molecular geneticshave yielded a specific genetic mutation identifi-able with a named bloodline. It is only a matter oftime before other heritable conditions in variousbloodlines likewise can be identified.

How is HYPP inherited inhorses?Based upon breeding trials conducted at the EquineResearch Laboratory at the University of Californiaat Davis, it was determined that HYPP is inherited asan autosomal dominant trait, which means it canoccur in both males and females. The trait is inherit-ed from generation to generation with equal frequen-cy; it does not get “diluted” out. Breeding an affectedheterozygous horse (N/H) to a normal horse (N/N)will result in approximately 50 percent normal off-spring, while 50 percent will carry the defective gene(N/H). Breeding an affected homozygote (H/H) willresult in all offspring carrying the gene mutation,regardless of the status of the other parent.

Normal (N/N) offspring can be safely bredwithout fear of HYPP being inherited. Selectivebreeding to normal (N/N) horses could entirelyeliminate HYPP disease. As HYPP is inherited as adominant condition, it can and is being spread toother breeds. It is to everyone’s benefit to take thenecessary steps to selectively breed HYPP out ofexistence before it becomes so widespread that thisis impossible.

Current Facts about hyperkalemic periodic paralysis (HYPP)A series of questions and answers released by the University of California, Davis

by Dr. Sharon J. Spier, DVM, PhDReprinted from The Quarter Horse Journal, April 1993

Clinical signsof HYPP dovary widely

amongdifferent

horses.

Can horses be tested for HYPP?A DNA test now has been developed and presentlyis available at University of California at Davis toidentify horses carrying the defective gene causingHYPP. This test detects the presence or absence ofthe specific genetic mutation which has been foundin the extended pedigree of Impressive descen-dants. From a sample, a part of the gene coding forthe horse muscle sodium channel is amplified, cut(using enzymes which cut specific DNAsequences), separated by electrophoresis, stainedand read. Based on the number of DNA fragmentsobserved, it can be determined whether the horsedoes not carry this specific mutation (a normalhorse), or whether it carries one to two copies ofthis abnormal gene mutation (heterozygous orhomozygous for HYPP, respectively).

How accurate is the DNA testfor HYPP?The test is accurate and reliable based uponresearch studies. The presence of the genetic muta-tion has been found to be associated with the dis-ease in more than 600 animals tested to date. In aprior publication (Nature Genetics 1992, Volume2, p. 144-147), we reported upon our testing of 51related horses which were diagnosed with HYPPbased upon documented episodes of muscle fascicu-lations or paralysis not induced by exercise. All 51horses were positive (for the sodium channel muta-tion) using this test. An equal number of relatedhorses which were determined to be normal (basedupon potassium challenge and/or free clinical signsof muscle disease) were negative for the gene muta-tion. We also tested 130 horses from five differentbreeds to determine if the mutation could be foundwith any frequency in the general horse population.The only horses to date which have shown themutation have been descendants of Impressive but,theoretically, other mutations may exist for whichwe now have the tools to start looking. The testhas proven to be repeatable, as we routinely re-runsamples (every sixth sample is repeated as part ofquality control) and we have not encountered anydiscrepancies in results following retesting.

Are false negative or falsepositive HYPP test resultspossible?“False” negatives: Of the 600 horses tested, we haveencountered four horses which show various clini-cal signs of muscle disease but are negative for thespecific gene mutation in the sodium channel. Allare privately owned horses which we have beenunable to study thoroughly. None of these horseshave demonstrated increased blood potassium con-

centrations in association with abnormal clinicalsigns. Two of these horses had markedly high mus-cle enzyme measurements, and one horse hadmarked muscle damage evident on muscle biopsy.We feel at this time that these horses probably haveanother muscle disease and not HYPP. We aresequencing the sodium channel for these four hors-es to determine if a second mutation actually exists.

“False” positives: We have not identified anyhorses which carry the gene mutation and do notcarry the disease. Of 142 samples we have receivedaccompanied by clinical information, approxi-mately 10 percent of the positive horses have notshown abnormal clinical signs (according to theirowners). All have been young horses (age four orless). None of these horses have tested negative byother means (such as response to potassium chal-lenge or electromyography).

No diagnostic test is 100 percent accurate.Errors feasibly could occur by several means. If thetest results conflict with clinical data, then it is pos-sible that the sample was mislabeled, or mishandledin the laboratory. Retesting should be performed.However, based on the results to date, we can saywith confidence that the presence of the mutationis the cause of HYPP, and the test is accurate andreliable. The test is extremely specific, and is accu-rate for the gene sequence substitution which hasbeen shown to cause HYPP in descendants ofImpressive. Theoretically, it is feasible that a differ-ent horse bloodline could have a mutation inanother portion of the sodium channel whichmight produce a similar form of muscle disease andnot be detected by this test. If this occurs, carefuldocumentation of the clinical signs and corre-sponding laboratory results (including serum potas-sium and muscle-derived enzyme concentrations)should be used to confirm the diagnosis.

Which horses should betested for HYPP?As noted above, the DNA test for HYPP identifiesthe specific genetic mutation which we now knowexists in descendants of Impressive. We presentlydo not know whether different genetic mutationsin other bloodlines also cause HYPP, and the DNAtest will not identify other such mutations. Furtherscientific research is required as to other blood-lines. We presently recommend that all descen-dants of Impressive be tested for diagnostic,treatment and breeding purposes.

Are HYPP test resultsconfidential?Test results are treated as confidential at our facili-ty. We notify owners or veterinarians (whorequest the test) of the results by mail.

A DNA testnow has beendeveloped andpresently isavailable... toidentify horsescarrying thedefective genecausing HYPP.

Do horses outgrow HYPP?No, an affected horse is affected for life, but symp-tomatology does seem to decrease with age. Thedisease also appears to be associated with periods ofstress, transport, concurrent diseases, initiation oftraining or intensive training, and dietary changes.It is possible that older horses do not experiencethe same degree of stress as young horses (i.e, theyare not subject to the rigorous show schedules ofyounger horses, and their owners have discoveredthe best diet and management routines for theseolder horses).

Can effective treatment berendered to HYPP afflictedhorses?HYPP in horses can be managed, and incidents ofmortality significantly reduced, by proper diet andthe administration of medication. While furtherstudies on the mortality rate of HYPP are required,it is important to put HYPP into perspective rela-tive to the many other conditions afflicting horses.Horses afflicted with HYPP, if properly managed,can lead productive, useful lives, and bring theirowners many hours of pleasure.

The first step towards effectively managingHYPP is to have the disease properly diagnosed. Itcan be confused with other conditions, such as“tying up.” It is essential that you consult withyour veterinarian if you wish to ascertain whetheryour horse has HYPP. We recommend the DNAblood test as the most effective and reliable meansof diagnosing HYPP.

What emergency treatment isrecommended for acuteattacks of HYPP?For a mild attack (when the horse is not down buthas muscle tremors), one or more of the followingemergency treatments are recommended:

• Exercise the horse, either by walking or lunging. Exer-cise stimulates adrenaline which helps replace potassi-um inside cells. However, use caution, as the horsecould stumble and fall while sustaining muscletremors.

• Feed grain (oats, dry corn-oats-barley or light Karosyrup for glucose supplement). Feeding carbohy-drates supplies glucose which stimulates the release ofinsulin and promotes potassium uptake by cells.

• Administer acetazolamide orally (3 mg/kg). This isusually six to eight tablets if the tablets are 250 mgeach. Acetazolamide increases potassium excretionfrom the kidney and also affects glucose metabolism.

For severe attacks, immediate veterinaryattention is necessary. If the horse is down andunable to stand, have your veterinarian:

• Place intravenous (IV) catheter and administer 23percent calcium gluconate (150 cc in one to two litersof five percent glucose/500 kg horse). The majority ofhorses respond immediately to this and stand up.

• If no response, follow with one L five percent sodiumbicarbonate IV (dose is one meg/kg).

• Still no response, give three L five percent dextrose IV,and monitor potassium levels in blood.

All of these treatments help stabilize the mus-cle membranes and lower blood potassium. Yourveterinarian should draw a blood sample prior toinitiation of treatment in order to analyze theblood potassium and muscle enzyme concentra-tions. This is required to confirm that the horsewas suffering an attack of HYPP and not some-thing else (i.e., colic).

What management practiceswill help control HYPP?The following management practices will greatlyassist in the control of HYPP:

• Establish a regular feeding and exercise schedule.Avoid fasting and water depreciation. Horses do bet-ter if allowed access to a paddock or pasture ratherthan strict stall confinement. Daily or nightly turnoutis helpful.

• Adult horses do very well on grass or oat hay alone orpasture. If it is necessary to use alfalfa to balance theration for growing horses, then mix alfalfa with grasshay or oat hay and grain (oats are best) to decreasepotassium content of diet. Feed equal amounts of hayand grain two or three times daily. Avoid rapidchanges in diet. Provide access to a white salt block orfeed loose salt.

• Administer acetazolamide (Diamox), a diuretic (2mg/kg orally twice a day). Many halter horse ownerscontinue to feed alfalfa hay as the only roughage, butmaintain their horses on this drug for all or most oftheir lives. Please note that this drug is a forbiddensubstance at horse shows under AQHA and AHSAregulations.

• Inform your veterinarian of HYPP condition prior toany general anesthesia, which may precipitate anepisode of paralysis. Maintain acetazolamide therapybefore and after surgery or anesthesia.

• Use common sense while hauling. Be sure to stop andwater horses frequently (every two hours). Acetazo-lamide treatment is helpful to prevent problems.

What is AQHA’s position onHYPP?AQHA recognizes that HYPP disease exists in theQuarter Horse breed and has contributed funds toour research to better understand its heritability

HYPP inhorses can be

managed,and incidents

of mortalitysignificantlyreduced, byproper diet

and theadministrationof medication.

and to develop improved methods of diagnosis andcontrol. The Association discussed HYPP at the1993 AQHA Annual Convention and determinedthat AQHA will fund $100,000 in additionalresearch on HYPP, and continue to inform andeducate AQHA members on the condition. In thefuture, the Association will determine what officialpolicies, if any, will be adopted by the membership.Owners and breeders should possess all currentlyavailable facts about HYPP before making deci-sions about their breeding programs.

At this point in time, testing horses for HYPPis a voluntary procedure by concerned owners andbreeders who wish to utilize the results to identifyhorses which may require dietary changes andmedication, and to reduce the disease in subse-quent generations. Important issues to be resolvedby AQHA and its membership concerning HYPPinclude the development of blood test protocols;the promulgation of disclosure requirements forsellers, breeders and owners; regulations coveringdrugs (such as acetazolamide) used to controlHYPP; foal registration requirements (if any); andrelated issues. Persons interested in these issuesshould contact AQHA.

EDITOR’S NOTE:Since the publication of this article in 1993,AQHA rules concerning the disclosure of HYPPhave changed. Foals born on or after January 1,1998, which descend from any bloodline deter-mined to carry the HYPP gene will have the fol-lowing notification placed on their registrationcertificate:

“This horse has an ancestor known to carryHYPP, designated under AQHA rules as a genet-ic defect. AQHA recommends testing to confirmpresence or absence of this gene.”

If the parent(s) tracing from the HYPP linetests negative for HYPP with an appropriate des-ignation appearing on the registration certificate,the above notification is not required and will besubstituted by the designation “N/N.” In addi-tion, once a foal has tested negative for the gene,owners can purchase a corrected registration cer-tificate which substitutes the designation “N/N”for the notification.

Any foals required to be parentage verifiedbefore registration, who trace to bloodlines knownto carry the HYPP gene, will be tested for the dis-ease at the same time genetic testing is performed.The results will be designated on the registrationcertificate in lieu of the above notification. Begin-ning with the 2007 foals, all Impressive progeny arerequired to be parentage verified and HYPP testedsubject to the conditions listed in rule 205. Any thattest H/H will not be eligible for registration.

AQHA recog-nizes thatHYPP diseaseexists in theQuarter Horseand has con-tributed fundsto...betterunderstand itsheritabilityand to developimprovedmethods ofdiagnosis andcontrol.

HYPP: Another LookReprinted from The Quarter Horse Journal, May 1993

During the past year, hyperkalemic periodic paraly-sis has become a major issue with the membership ofthe American Quarter Horse Association. Themajority of the concern has centered around notknowing what the disease is or how it can be con-trolled. It was those same concerns that promptedthe AQHA Research Committee, in 1989, to fund aproject at the University of California, Davis.Another project on HYPP was funded in 1991, thisone with the University of Pennsylvania.

The results of the University of Californiaresearch project were printed in the September1992 issue of The Quarter Horse Journal. Duringthe next couple of months, concern, speculationand rumors about the condition abounded,prompting an official statement of position byAQHA. Published in the December issue of TheQuarter Horse Journal, the statement noted thatthe disease affects only a small percentage of the

total horses registered by AQHA, and that itappeared to be limited to individuals from onebloodline. It also said that most of the individualsaffected were bred for halter competition.

In the January 1993 issue of The Quarter HorseJournal, it was reported in “AQHA Update” thatDr. Sharon Spier of UC, Davis, had acknowledgedthat in her research, all horses found with the dis-ease were descendants of the Quarter Horse stal-lion Impressive. Dr. Spier revealed the stallion’sname while responding to questioning following atalk she presented on HYPP at the AmericanAssociation of Equine Practitioners meeting onNovember 30, 1992.

Articles on HYPP have now appeared inevery major horse publication, and in many dailynewspapers, including the New York Times .Much of the information reported was in error,and has blown out of proportion the effect the

disease is having on the American Quarter Horsebreed. The Association has acknowledged theexistence of HYPP and that so far the disease hasbeen found only in one bloodline. However, atthe 1993 AQHA Convention in March followinga discussion with UC Davis’, Dr. Spier, the StudBook and Registration Committee felt that notenough was known about the disease for theCommittee to make any recommendations eitherway, and asked the AQHA Executive Committeeto fund further research into the disease at theUniversity of California, Davis.

“It is important to put HYPP into perspec-tive relative to the many other conditionsaffecting horses,” said Dr. Spier. “Horses afflict-ed with HYPP, if properly managed, can leadproductive, useful lives, and bring their ownersmany hours of pleasure.”

What is HyperkalemicPeriodic Paralysis?Hyperkalemic periodic paralysis is a muscular dis-ease caused by a hereditary genetic defect, which,simply put, affects the muscle cells’ balance ofsodium and potassium.

The genetic defect disrupts the normal open-ing and closing of a tiny passageway in the mem-brane of muscle cells, allowing sodium to flow inand potassium to flow out of the cell in an irregularmanner. The influxes change the voltage currentof muscle cells, causing uncontrolled muscletwitching or profound muscle weakness. High lev-els of potassium in the blood can be associatedwith an attack.

The genetic defect which causes HYPP wasthe result of a gene mutation. Gene mutations areconstantly occurring, but the majority of thosewhich prove to be detrimental to the species inwhich they occur are not compatible with survival.However, this mutation happened in an animalwhich was to become a popular type for haltercompetition, and it not only survived, it was con-tinually reproduced.

In breeding trials at UC Davis, it was deter-mined that HYPP is inherited as an autosomaldominant trait, which means that it is not sex-l inked — it can occur in both males andfemales. The trait is inherited from generationto generation with equal frequency; it does notget “diluted” out.

Those carrying the defective gene are eitherheterozygous, which means that only one of thetwo sets of genes inherited from their parents isaffected, or homozygous, where both sets of genesare affected. When a heterozygous individual isbred to a normal horse, approximately 50 percent

of the offspring will carry the defective gene.Breeding two heterozygous animals will result in75 percent of the offspring being affected. One-fourth of the offspring of such a mating arehomozygous for the defective gene, and one-fourthare normal.

Researchers at UC Davis have found only onepercent of the horses they have tested to behomozygous affected. Breeding an affectedhomozygous animal will result in all offspring car-rying the defective gene, regardless of the status ofthe other parent.

A DNA test is available at UC Davis, to iden-tify horses carrying the defective gene. If a horsetests positive for the genetic mutation, the test willalso determine whether it is heterozygous orhomozygous. The foals from heterozygous matingsthat do not receive the defective gene can be bredwithout propagating HYPP. It is possible to totallyeliminate HYPP resulting from this identifiedmutation by breeding only those individuals withnegative blood tests. A similar condition exists inhumans, where several different mutations havebeen found to cause the disease. The current testfor horses is highly specific for one mutation whichhas been identified in association with HYPP.

Symptomatology of HYPPIn most cases, symptoms of the disease includeintermittent muscle tremors or twitching. In someinstances, horses lose complete muscle control andcollapse. Occasionally, episodes are accompaniedby respiratory noises resulting from paralysis of themuscles of the larynx and pharynx.

In rare cases, death may occur, usually fromcardiac arrest and/or respiratory failure.

Attacks of the disease may be associated withperiods of stress, transportation, concurrent diseaseand training, or by a dietary change, in particularthe ingestion of potassium in feed. Alfalfa hay isvery high in potassium, as is molasses, a significantingredient in most sweet feeds. High levels ofpotassium in the bloodstream are not only indica-tive of an attack of HYPP, but may also triggerattacks. Stress causes a release of potassium intothe bloodstream, as does the ingestion of alfalfa orother feeds high in potassium.

Metabolic pathways of HYPPHyperkalemic periodic paralysis is a muscular dis-ease caused by a hereditary genetic defect whichserves to disrupt the normal operation of the sodi-um ion channel in cells. The sodium ion channelis a tiny passageway in the membrane of musclecells which controls the movement of sodium par-

Hyperkalemicperiodic

paralysis is amuscular

disease causedby a hereditarygenetic defect,which, simply

put, affectsthe muscle

cells’ balanceof sodium and

potassium.

“HYPP inhorses can bemanaged, andincidents ofmortalitysignificantlyreduced, byproper diet andadministrationof medication.”

ticles in and out of the muscle cell.There is normally a low concentration of sodi-

um inside muscle cells, and a high concentrationon the outside. This difference determineswhether or not a muscle is relaxed or contracted.Naturally occurring electrical charges exist in allmuscle cells, and sodium particles carry a chargethat changes the voltage current of a muscle cell,allowing it to contract or relax. In horses affectedwith HYPP, the regulation of particles through thesodium channel occasionally fails, which disruptsthe normal flow of ions in and out of the musclecells. The result is uncontrollable muscle twitch-ing or complete muscle weakness.

Potassium, too, plays a part in the defect.Every cell in the body contains potassium, as it isvital for maintaining the cells’ volume and the“charge” in excitable tissues such as muscle cells.In an opposite relationship as that of sodium, theconcentration of potassium on the inside of cells ismuch higher, up to 25 times, than on the outside.The “leaky” cell membranes in horses with HYPP,which allow sodium to pass through, also allowpotassium to pass, resulting in a higher concentra-tion of potassium in the blood than is normal.

Minor changes in voltage (depolarization)can occur due to increases in the potassium con-centration outside of the cell, such as might occurfollowing ingestion of large amounts of feed highin potassium - alfalfa hay for instance. As singlemuscle fibers depolarize, they communicate thischarge to surrounding fibers, leading to visiblemuscle tremors. If enough fibers depolarize, mus-cle paralysis and collapse will occur. When themuscles depolarize, potassium from inside the mus-cle cells moves to the outside of the cells, leadingto further increases in potassium concentration inthe blood, which helps perpetuate the cycle.

If your horse has HYPP...“Having a positive test for the hyperkalemic peri-odic paralysis is not necessarily fatal,” according toDr. Spier. “HYPP in horses can be managed, andincidents of mortality significantly reduced, byproper diet and the administration of medication.”

Mild attacks can normally be handled by theowner. Sometimes exercising the horse will causethe symptoms to disappear, and in other instances,the administration of acetazolamide, a mild diuret-ic that increases potassium excretion from the kid-neys, will return the horse to normal. More seriousattacks should be handled by veterinarians.

To be certain that the symptoms indicatethe presence of HYPP, a veterinarian shoulddraw a blood sample prior to initiation of treat-ment in order to analyze the blood potassiumand muscle enzyme concentrations. Some cases

of colic have been confused with attacks ofHYPP, and vice versa. According to Dr. Spier,“There may be some room for misdiagnosis, orover-diagnosis. Every horse that trembles or tiesup does not have HYPP.”

Owners with horses that have tested positivefor the condition may want to have their horses ondaily doses of acetazolamide as a preventative.They should be aware, however, that acetazo-lamide is a prohibited substance for any horse com-peting in an AQHA-approved event.

Several management practices may alsohelp control the disease, including regular feed-ing schedules and continuous access to water.Horses on pasture do better than those confinedto stalls, and rations should contain as littlepotassium as possible.

Roy Donn of Crosby Farms in Aubrey, Texas,has been dealing with HYPP since 1985, when ahorse he had just purchased had an attack whilebeing unloaded from a van. Since then he hashandled a number of positive horses, and says thatit does not pose too big of a problem.

“We have dealt with a lot of them and havenever had one die,” he said. “The reason is that ifwe see any symptom of HYPP, we start the horseon medication and never take him off of it.”

Dr. Spier recommends a dosage of four to six25-milligram acetazolamide tablets twice a day.Donn noted that for a large horse, he gives sixtablets, twice a day, but that on some exceptional-ly large animals, he has given up to eight tablets.

“I don’t think we’ve ever treated anythinguntil after it was weaned,” he said, “and very few ofthem. But you put them in a stressful situation andit will show up. With babies, we give two or threetablets, on up to six as they get older.”

Donn says that he feeds his horses straightoats, which are low in potassium, but he also feedsalfalfa hay. He says that the acetazolamide controlsthe disease, even when the animals are on alfalfa.

What now?At the 1993 AQHA Convention in March, Dr.Spier appeared before the open session of the StudBook and Registration Committee and answerednumerous questions concerning HYPP. She alsoattended the closed meeting of the Committee,and pointed out that there were still a number ofunanswered questions about the disease. The con-sensus of the Stud Book and Registration Commit-tee was that further research was needed to betterunderstand the disease, and perhaps, its control.At its April meeting, the AQHA Executive Com-mittee approved the request for funding thatresearch.

For More Information...Many persons have requested a list of publications on HYPP. AQHA’s official publications, including The Quarter

Horse Journal, are excellent resources on issues affecting the American Quarter Horse breed and the industry. Subscriptioninformation can be found on the back cover of this brochure.

The following are publications/articles on equine hyperkalemic periodic paralysis:

Severalmanagement

practices mayalso help

control thedisease,

includingregular feedingschedules and

continuousaccess to

water.

Dr. Spier said recently there were severalareas that UC Davis was hoping to research,including trying to get as accurate a set of statisticsas possible on the number of horses affected by thedisease; why there are ranges in degree of severityof those affected, even among families; and whysome horses appear to be asymptomatic, eventhough they have tested positive for the gene.

She said, “The disease is very complicated,because management, training and feed all play abig role in whether or not a horse shows symp-toms.”

Dr. Spier also noted that they were initiatinga study on testing embryos and fetal cells forHYPP. That way, she said, if an embryo is deter-mined to be positive, the owner has the option ofaborting the mare and rebreeding her.

“We’re also going to be looking at where thedisease came from,” she said. “No one here hasever said that the disease originated with Impres-sive, contrary to what has appeared in some of themedia. All of the horses to date that we havefound to have the disease did trace back to Impres-sive, but we are going to screen some related andnon-related horses to see if we can find the condi-tion existing in another bloodline. We hope to

screen at least 1,000 horses in this project.”Dr. Spier concluded by emphasizing that

research takes time. It took years to find out whatis now known, and any further discoveries will nothappen overnight. However, if and when addi-tional information is learned, it will be made avail-able in order to allow owners the opportunity tomake responsible decisions about their horses.

EDITOR’S NOTE:Since the publication of this article in 1993,researchers at the University of California,Davis, have completed a screen of 1,000 samplesto test for HYPP gene frequency. The resultsfrom this research, as well as an update on otherHYPP research, can be found in the article“HYPP: Someone else’s problem” by LesliGroves, which appears near the front of thisbrochure.

Since the publication of the articles appearing inthis brochure, the preferred sample to perform anHYPP test at the University of California is ahair sample.

• Cox, J.H., DeBowes, R.M. “Episodic weaknesscaused by hyperkalemic periodic paralysis inhorses.” Comp Cont Educ Pract Vet (Equine)1990; 12:83-89.

• Naylor J.M., Robinson J.A., Bertone J. “Familialincidence of hyperkalemic periodic paralysis inQuarter Horses.” J Am Vet Med Assoc. 1992;3:340-343.

• Pickar J.G., Spier S.J., Snyder J.R., et al.“Altered ionic permeability in skeletal musclefrom horses with hyperkalemic periodic paraly-sis.” Am J Physiol (Cell Physiol) 1991;260:C926-C933.

• Rudolf J.A., Spier S.J., Byrns G. Hoffman E.P.“Linkage of hyperkalemic periodic paralysis inQuarter Horses to the horse adult skeletal mus-cle sodium channel gene.” Animal Genetics1992, 23:241-250.

• Rudolf, J.A., Spier, S.J., Byrns, G. Et al. “Period-ic paralysis in Quarter Horses: a sodium channelmutation disseminated by selective breeding.”Nature Genetics 1992; 2:114-147.

• Spier S.J., Carlson, G.P. “Hyperkalemic period-ic paralysis in certain registered Quarter Hors-es.” The Quarter Horse Journal, September1992, p.p. 68-69, 120.

• Spier, S.J. Carlson, G.P., Holliday, T.A, et al.“Hyperkalemic periodic paralysis in horses.” JAm Vet Med Association 1990; 197:1009-1017.

• Steiss J.E., Naylor J.M. “Episodic muscle tremorsin a Quarter Horse: Resemblance to hyper-kalemic periodic paralysis.” Cn Vet J 1986;27:332-335.

HYPP TEST

To have your horse tested for HYPP, please complete the blanks below and mail it to ouroffice with the $40 testing fee (U.S. Funds Only). Once we receive this, we will send youa hair collection kit with complete instructions. Telephone orders will be taken if you wishto pay with a Visa, MasterCard or American Express.

American Quarter Horse AssociationP.O. Box 200

Amarillo, TX 79168Telephone: 806-376-4811

The results will be placed on the horse’s permanent records. Having N/N results on filemay prevent any future offspring from having to be tested.

Horse’s Name and Registration Number:

If unregistered, list dam’s name and year foaled:(registration application must be in our office before a kit can be sent)

Name of person to whom kit is to be mailed AQHA ID Number

Complete Mailing Address

City, State and Zip Code Daytime Telephone Number

To pay with a Visa, MasterCard or American Express, complete the following information:

—– —– —– —– / —– —– —– —– / —– —– —– —– / —– —– —– —– - —–/—–Card Number Expires

Cardholder’s Name AQHA ID #, if known

Cardholder’s Complete Address Daytime Telephone Number

City, State and Zip Code Signature

If you wish to have your horse tested confidentially (or if you wish to test a horse that isnot registered with AQHA), you may contact the University of California at Davis directly.Their fee for testing is $50.

Veterinary Genetics LaboratoryHYPP Testing

Old Davis RoadUniversity of CaliforniaDavis, CA 95616-8744

Telephone: 530-752-2211

Funding for Equine Research Projects

Each year, the American Quarter Horse Association awards hundreds ofthousands of dollars to college and university equine research programs tofund research that benefits all horses. That figure is a testament to the factthat AQHA is dedicated to a better understanding of the horse, as well as tohis future enjoyment by everyone.

AQHA represents more than 332,000 Members and some one million own-ers of American Quarter Horses worldwide. With a registry of more than 4million American Quarter Horses, AQHA recognizes the need for practicalequine research and increased knowledge of equine health care and treat-ment.

AQHA’s Equine Research Committee was founded in 1960 and comprisesleading American Quarter Horse breeders, veterinarians and individualswell grounded in equine research methods. Each year this committeereviews specific research funding requests from many colleges and universi-ties, selecting the most promising and appropriate projects to fund. Since1960 AQHA has awarded more than $4.5 million in research funds.

What type of Equine Research does AQHA support?

For funding consideration AQHA places a premium on research projectsthat address problems of prime importance to the general horse populationand to those people involved in the day-to-day management of horses.While any research that leads to a better understanding of equine disorders,diseases or nutrition can be beneficial, AQHA most readily supportsresearch that addresses areas of primary relevance to the most commonequine management issues and concerns.

AQHA research priority lists:

• Diagnosis and treatment of acute gastro-intestinal disorders (colic, etc.)

• Diagnosis and treatment of musculoskeletal defects of nutritional origin (OCD, epiphysitis, etc.)

• Diagnosis and treatment of reproductive disorders (endometritis, etc.)

• Immunization of foals • Diagnosis and treatment of infectious diseases of the gastro-intestinal

tract (potomac fever, salmonella, etc.)• Diagnosis and treatment of respiratory diseases (bleeders,

pneumonia, etc.)• Vesicular Stomatitis Virus (VSV)• Equine Protozoal Myeloencephalitis (EPM)

This list indicates types of research projects of significant importance tohorse owners and their priority in AQHA funding support. The researchareas indicated on the list are only guidelines to the type of research AQHAfeels is of most benefit and does not preclude the possibility that theAQHA Equine Research Committee would recommend approval of funding for any worthwhile areas of research.

The American Quarter Horse Journal

Stimulating feature articles on lifestyles,training and tips, health and management,plus popular columns such as Don Burt’s“On the Rail”, Baxter Black’s “On the Edge of Common Sense” and, of course, “Legends”.The American Quarter Horse Journal is alsoyour official connection to AQHA, telling youeverything you need to know about how tomake the most of your affiliation.

The American Quarter Horse Racing Journal

Industry news; reports on major races; profiles of successful owners, breeders, trainers and jockeys; articles on racehorsecare; history; results of major sales; commentary from industry leaders and more racing statistics that you can imagine.

A World of InformationToday’s world is based on information-we can provide it to you! Check out these official AQHA publications:

To subscribe to any of thesepublications, call us toll-free

at 1-800-291-7323