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From: jrdvmdiver@aol.com (JRDVMDIVER)
Date: 1995/04/03
EQUINE HYPERKALEMIC PERIODIC PARALYSIS (HYPP):
Julie A. Robinson, DVM, MVSc, MS, Dipl. ABVP (Equine)
HyPP =3D Muscular disease of horses (and humans) characterized by
intermittent episodes of muscular weakness, fasciculation,
tremors, or paralysis in association with hyperkalemia due to an
inherited genetic defect in the sodium ion channel. (ALSO KNOWN
AS "IMPRESSIVE SYNDROME")
SIGNALMENT =3D Usually well muscled Quarter Horses and Quarter Horse-cross
More stallions and geldings than females reported, not sex-linked
CS usually 1st seen ~2 years of age (range, neonates > 10 yrs)
Some older horses seem to improve but the condition is not one
that is "out grown"
HISTORY (Hx) =3D Owner reports: horse "faints", colics, seizures,
muscles"jump", tying up, recumbent
Usually horse is in training, often intensive
High potassium diet (alfalfa hay & molasses containing feeds)
Reported more in stalled horses than pastured horses
Stress associated with transport, general anesthesia, concurrent
diseases, intensive training or initiation of training,
dietary changes
CLINICAL SIGNS (CS) =3D
Vary from horse to horse, can range from most severe in
homozygous (H/H) horses to none in heterozygous (H/N)
horses, why this occurs is being investigated
Episodic/intermittent
Occur any time of day or night
Duration 30-90 min (range =3D 15 min-4 hrs)
Stress and/or increased serum potassium for any reason can
precipitate CS
PRODROMAL SIGNS =3D
restless / irritable
dull / depressed
increased urination / defecation
"anxious look"
ACUTE EPISODE =3D
3rd eyelid prolapse
sardonic grin
sweat
tachycardia
tachypnea
generalized muscle tremors / fasciculations (jaw, neck, shoulder,
flanks, thorax, abdomen, hind limbs)
muscle weakness
sawhorse stance with head down /inability to raise head
"dog sitting"
involuntary recumbency /inability to rise
usually conscious/aware but not able to respond
neurologic exam normal except for decreased reflex response
feels pain/cannot react
=F1increased muscle fasciculation associated with attempts to move
congested mucous membranes
dyspnea
dysphagia
arrhythmias-ECG changes; spiked T waves, loss of P waves, normal-
decreased Q-T segment, increased duration P-R interval,
prolonged QRS
=F1atrial fibrillation which converts as episode subsides
=F1ventricular flutter/standstill/death
CHRONIC/BETWEEN EPISODES =3D usually normal between episodes
=F1stiff
=F1"dimpling"
normal neuro exam
Electromyography (EMG)-increased insertional activity, increased
spontaneous activity-myotonic discharges, complex repetitive
discharges (doublets, triplets, etc), fibrillation
potentials, positive sharp waves
LABORATORY=3DPotassium ([K+]) normal between episodes, increased serum
[K+] during episode > 5 meq/l, (normal 3 - 5 meq/l), CS seen as
[K+] spikes, as [K+] decreases CS subside
Serum [Na+] decreases as [K+] increases
Calcium [Ca++], Magnesium [Mg++], acid:base status, glucose, renal
parameters are normal during & between episodes
=F1Mild increases in muscle enzymes (CPK & AST) following episode,
usually only if horse has been recumbent
Increased Packed Cell Volume/Total Protein (PCV & TP) - due to fluid
shift from extracellular to intracellular space (increases with
[K+] during episode)
RBC (intracellular) increased [Na+]/decreased [K+] (with CS)
In horses found dead - increased intraocular [K+] at necropsy
DIAGNOSIS (Dx) =0FHallmark =3D Increased serum/plasma [K+] with CS=0F
CS & increased [K+] induced with oral KCl:
1. Make sure no cardiac, renal or adrenal disease before giving KCl &
12hr fast (no CS if eats)
2. 0.08-0.13 gm/kg KCl in 200 ml H2O via nasogastric tube (40-70 gms)
(40 gms 1000# horse) affected horse will show CS in ~2hrs,
normal horse will not show CS (even at 3x's dose)
3. Check [K+] every 30 - 60 min, monitor horse continuously
4. Have treatment on hand in case episode is severe/treat anyway once
Dx is confirmed
EMG - increased insertional & spontaneous activity between episodes,
myotonic discharges, EMG findings useful in Dx along with Hx of
CS (Other myopathies can show similar findings on EMG)
GENETIC TESTING=0F SAMPLE=3DEDTA (PURPLE TOP) 10cc BLOOD COST=3D$35.00
VETERINARY GENETICS LABORATORY
HyPP TEST
SHARON J. SPIER, DVM, PhD, Dipl. ACVIM
DEPARTMENT OF MEDICINE RM 2121 MS1-A
SCHOOL OF VETERINARY MEDICINE
UNIVERSITY OF CALIFORNIA - DAVIS
DAVIS, CA 95616-8744
(916) 752-7416 (INFO) / 2211 (LAB) / 3558 (FAX)
Check payable to UC Regents or Visa, M/C, AMEX
May be additional charges from DVM who collects and ships sample
This test involves using a whole blood sample, amplifying part of the
gene code, cutting it with specific DNA enzymes, separation with
electrophoresis, staining it and then reading the sequence to detect
the absence or presence of the abnormality. The test can identify a
normal horse (N/N) or a carrier horse and tell whether or not the
carrier is heterozygous (N/H) or homozygous (H/H) for the defect. The
test has been described and reported as accurate with no false
positives and very few "false" negatives (horses that displayed
compatible CS but the defect was not found). It is recommended that
all horses descended from the particular stallion involved be tested
especially before using the animal in a breeding program. Test
results are confidential - results are NOT given out over the phone,
and the lab only notifies the owners and DVMs who request the test.
DIFFERENTIAL DIAGNOSIS (DDx) =3DIn DDX of HyPP consider breed/pedigree
time of occurrence of CS
response to treatment
lab results
muscle biopsy
Exercise hyperkalemia
Exertional rhabdomyolysis
Colic
Tetanus
Seizures /epilepsy
Hypomagnesemia /hypocalcemia
Post-anesthetic myopathy
Myotonia/myotonic dystrophy
Narcolepsy
TREATMENT (Tx)=3DPRODROMAL/MILD SIGNS =3D Karo syrup PO, walk, feed oats,
Give 3 mg/kg Acetazolamide (6-8 250 mg tabs), CALL DVM!
ACUTE/SEVERE EPISODE =3D (aim of Tx - decrease [K+] by increasing cell
uptake & excretion), CALL DVM!!!
PLACE IV CATHETER DRAW BLOOD FOR DIAGNOSIS ([K+] AND GENETIC TEST)
(1) 23% Calcium gluconate IV 0.2 - 0.4 ml/kg (91 - 182 ml/1000#)
150 ml in 1-2 L 5% glucose to 500 kg horse
(2) 5% Sodium bicarbonate IV 1 mEq/kg (454.5 mEq/1000#) 1 L
(3) 5% Glucose IV 6 ml/kg (2727 ml/1000#) 3 L
Insulin 0.1 Unit regular/kg IV (45.4 units/1000#) MUST be given
with glucose! (DO NOT give alone - will make horse hypoglycemic)
Epinephrine 3 ml 1:1000 IM (experimental Rx)
CONTROL/PREVENTION OF EPISODES=3DFeed 3-4 times/day, oats/oat hay, NaCl
block, NO alfalfa or molasses, Na+ Bicarb - 1 oz/feeding, REGULAR
FEEDING SCHEDULE, make diet changes slowly, NEW FEED
AVAILABLE=3DMontana Pride, HyPP diet, "nutraceutical" treatment,
ALFA CARE Plus H, < 1% Potassium, contains beet pulp shreds and
rice hulls, call 1-(800) 987-2532 for information
Regular exercise/turnout in pasture better than in stall
Stop and rest horses, provide plenty of water during transport
Acetazolamide (Diamox) 3.85 mg/kg PO BID-QID for 3 days, then 2.2
mg/kg PO BID-TID titrate dose for each horse, monitor [K+]
during Tx, AQHA AND AHSA FORBID COMPETITION ON THIS DRUG!!!
Thiazide diuretics (hydrochlorothiazide)
PROGNOSIS=3DProbably good for life if use dietary/exercise management
along with acetazolamide if needed. Some horses have been found
dead following an episode, most likely the result of cardiac
arrest and/or respiratory failure.
GENETICS=3DThe defect is most likely due to a single mutation occurring
as a normal result of evolution, which has been propagated by
breeders since this defect is associated with heavily muscled
horses that have performed very successfully in the show ring.
This defect has produced an abnormal but functional Na+ ion
channel. Normal horses-Phenylalanine (PHE) is present at a
particular location in the protein that codes for normal Na+
channel, HyPP horses-Leucine (LEU) is present at that same
location and codes for abnormal Na+ channel, Defect is NOT
because abnormal K+, But CS are result of abnormal K+ due to the
abnormal Na+ channel, inherited as an autosomal dominant trait
with incomplete penetrance, found in one QH bloodline,
recommended that owners not breed affected horses, any time a
Pre-purchase Exam is requested on a QH or QH-X that has this
bloodline the UCD genetic test should be performed. A horse that
carries the abnormal gene can pass the defect on to their
offspring whether the parent horse has shown clinical signs or
not. A N/N (normal) horse bred to a heterozygous (N/A) will have
50% affected offspring and breeding a homozygous (A/A) will
result in 100% affected offspring. The only way to eradicate the
disease is to test, identify, and breed only normal horses of the
affected bloodline. To date HyPP has only been identified in the
descendants of one QH stallion. This is an extremely popular
bloodline, thus the defect has become widespread in QHs and QH
crosses. Research is underway to check other bloodlines for the
defect or possibly another defect which could produce similar
signs. There have been anecdotal reports of similar signs in a
family of Arabians.
ETIOLOGY/PATHOGENESIS=3DETIOLOGY=3DHyPP is a genetic Disease.
PATHOGENESIS=3DMechanism was poorly understood, Now thought to be a
muscle membrane defect resulting in loss of K+ from the cell due
to an abnormality in the Na+/K+ pump (defect in the voltage-gated
Na+ ion channel) & impaired K+ transport & neuroendocrine
regulation. The Na+ ion channel is a protein "gate" in the
muscle cell membrane. The genetic defect alters the normal
function of this channel such that it no longer opens or closes
normally. This defect is not incompatible with life but does
interfere with normal muscle function and regulation of Na+
within the cell and K+ outside the cell. It also makes the cell
membrane more sensitive to increases in extracellular [K+]. The
abnormality in the Na+ ion channel allows increased Na+ influx
into the cell and increased K+ out of cell resulting in altered
voltage of the muscle cell membrane potential leading to
uncontrolled twitching of the cell which is then transferred to
surrounding cells resulting the tremors and weakness that are
manifested as clinical signs.
LIABILITY =3D The AVMA Professional Liability Insurance Trust has made
the following recommendations:
1. Discuss with client the nature of the disease HyPP.
2. Discuss with client the bloodline(s) involved.
3. Explain and recommend the UCD genetic test.
(If owner refuses genetic testing have them sign a statement
stating that it has been explained to them and they
chose not to run the test)
4. If diagnosis is confirmed discuss clinical signs.
5. If diagnosis is confirmed discuss treatment options /
effectiveness.
6. If diagnosis is confirmed discuss genetic implications of
breeding.
7. If diagnosis is confirmed discuss risks of owning / working
with positive horses (i.e. possible collapse "on" owner /
rider / handler)
AMERICAN QUARTER HORSE ASSOCIATION (AQHA):
1. Has and continues to fund HyPP research.
2. Has not yet set any specific guidelines regarding testing,
showing or breeding, other than to disallow competition on
acetazolamide
3. Hypp research continues
SUMMARY=3DHyPP is a genetic disease of Quarter Horses and Quarter Horse
crosses (to date descended from 1 Quarter Horse stallion) that
results in a primary myopathy. The clinical signs of muscle
fasciculation are seen in association with hyperkalemia. First
described in 1985, more and more cases are being diagnosed as
veterinarians and owners become aware of the condition.
Treatment is aimed at decreasing potassium by decreasing intake
and increasing cell uptake and excretion. The disease can be
managed but some horses die as a result of the detrimental
effects of hyperkalemia. Eradication of HyPP is possible only
through breeding of horses shown not to be carriers of the
genetic defect. A carrier horse is just a capable of passing the
defect whether that individual shows minimal or severe CS. At
this time AQHA has and is funding further research, AQHA has not
developed any official policy regarding the testing of horses for
HyPP or the status of positive horses
ADDRESS-EQUINE HYPERKALEMIC PERIODIC PARALYSIS (HyPP) GENETIC TEST:
VETERINARY GENETICS LABORATORY
HYPP TEST
SHARON J. SPIER, DVM, PhD, Dipl. ACVIM
DEPARTMENT OF MEDICINE RM 2121 MS1-A
SCHOOL OF VETERINARY MEDICINE
UNIVERSITY OF CALIFORNIA - DAVIS
DAVIS, CA 95616-8744
(916) 752-7416 (INFO), (916) 752-2211 (LAB)
(916) 752-3558 (FAX)
SAMPLE =3D EDTA (PURPLE TOP) 10cc BLOOD
LABEL TUBE WITH HORSE NAME &
REGISTRATION NUMBER
OWNER/AGENT
LABEL PACKAGE: HyPP
INCLUDE LETTER REQUESTING HyPP TEST
WITH: PEDIGREE/COPY PAPERS
(SIRE & DAM)
COST =3D $35.00 VISA, M/C, AMEX OR
CHECK PAYABLE TO: UC
REGENTS/VETERINARY GENETICS LAB
ADDITIONAL INFORMATION:
AMERICAN QUARTER HORSE ASSOCIATION (AQHA)
P.O. BOX 200
AMARILLO, TEXAS 79168
(806) 376-4811
Recent JAVMA articles, Journal of the AQHA articles, recent equine or
large animal texts.
^^^^^^^^^^
HYPP - Defective Gene Concerns QH Breeders
Hyperkalemic periodic paralysis (HYPP) has become the subject
of research, discussion and concern among American Quarter
Horse Association members. As many as 60,000 registered
Quarter Horses out of 2.9 million nationally have an uncommon
gene that causes HYPP.
Researchers at the University of Pittsburgh School of
Medicine discovered the defective gene. The gene, which
causes a disruption in the muscle cell metabolism, was found
while isolating it in a new diagnostic test.
Thie cell disruption has led to muscle paralysis, collapse
and death in Quarter Horses. The bloodline that carries this
gene was traced to the Quarter Horse stallion Impressive, who
has 40,000 descendents. This one stallion was coveted for
breeding purposes for 25 years because of his well-developed
build and world championships. The disease has become
commonly known as the "Impressive syndrome".
Wendy Winans of Bo-Bett Farm in Reddick, FL, believes the
spread of this disease has been caused by excessive
inbreeding to the Impressive line by breeders desirous of
heavily muscled halter horses. The symptoms are manifested
at a much lower level in performance horses.
Dr. Eric Hoffman, assistant professor of molecular
genetics/biochemisty/human genetics at Pittsburgh, and
various co-authors including Dr. Sharon Spier of the
University of California, Davis, first reported their
discovery in an article featured in Nature Genetics.
According to Hoffman, HYPP occurs when channels in the muscle
cell membrane do not conduct electrical impulses correctly
and the cell malfunctions, causing paralysis that can last
from minutes to days.
"We found the disease was caused by a single amino acid
substitution in the gene. Voltage-sensitive channels
participate in all actions involving thought and movement,"
Hoffman said. "This is the first genetic problem involving
one of these channels to be uncovered."
The lethal disruption takes place when a QH with the
defective gene ingests food high in potassium and/or by
exercising. Alfalfa, fescue, timothy, and clover hays are
all high in potassium, but the biggest culprit is molasses,
sugar beet and sugar cane. Carrots are also high in
potassium but it is doubtful that any horse will be fed
enough carrots to manifest the symptoms.
The disease is characterized by intermittent episodes of
muscle tremors, manifested by generalized or localized
shaking, trembling and weakness. In mild attacks, muscle
tremors may be so subtle as to be detectable only by an
experienced clinician performing EMG testing. Occasionally,
episodes are accompanied by respiratory noises resulting from
paralysis of the muscles of the upper airway (larynx and
pharynx).
Hoffman explained that the spasms can be slow, gentle ones
that relax when potassium is eliminated or they can be sudden
and violent resulting in unpredictable attacks of paralysis,
erratic and irregular heartbeats, or immediate death. The
cause of death is usually cardiac arrest but can also be
complicated by respiratory paralysis and failure.
Clinical signs of HYPP vary widely among different QH.
Homozygous horses (that have the defective gene at both loci
on the chromosome) are affected more severely than
heterozygous horses (who have one normal and one defective
gene on the chromosome). The disease manifests itself early
in life and is usually diagnosed between ages 2 and 15. The
problem is there from birth.
Under ideal management practices, the defective gene does not
appear to have adverse effects. But, stress or increased
potassium in the serum can trigger clinical signs of muscle
dysfunction. If the disorder is not lethal, it can be
somewhat controlled through diet and diuretics such as
acetazolamide. If managed, incidents of mortality can be
significantly reduced.
Currently, the AQHA suggests changes in management practices
to assist in controlling HYPP. These changes include
establishing a regular feeding and exercise schedule, avoid
any fasting and water depreciation, and giving horses access
to paddocks or pastures rather than confining them to stalls.
Adult horses do very well on grass or oat hay rather than an
alfalfa mix which can intensify or aggravate the disease.
Why some horses manifest severe signs of the disease and
others exhibit little or no signs is yet unknown, but is
under investigation. Most QH breeders and owners are deeply
concerned with this issue and the public's response to it.
The AQHA has received many complaints about QH professionals
being permitted to advertise their horses with Impressive
bloodlines and breeding services of these horses in trade
journals.
"As of this time, there are no regulations in regard to
mandatory testing, breeding or registration of affected
horses," said Gary Griffith, AQHA spokesperson and registrar.
1/28/94
Good Luck IMHO O-) Dr JR
All Standard Disclaimers Apply...
---------------------------------------
Update From: mjjacks@why.net(Marcy Jackson)
Date: May 1996
"AQHA Rulings Regarding HYPP"
In 1997, AQHA will include HYPP as part of the "Genetic Defects
and Undesirable Traits" which also includes parrot-mouth and=20
cryptorchid conditions. Beginning with foals born in 1998, foals=20
descending from the stallion Impressive or any other bloodline=20
determined to carry the HYPP gene will have a notifiation placed on
their registration certificates. The notification will state that the=20
foal comes from bloodlines known to carry the HYPP gene and that
AQHA recommends testing to confirm the presence or absence of=20
this gene. =20
The notification will not be required once the parent(s) tracing=20
from the HYPP line has tested negative for HYPP. The designation
"N/N" will replace the notication for foals descending from these
bloodlines. If a foal tests negative then the registration certification
with the notification may be replaced with the "N/N" designation. =20
All 1999 foals and later will be parentage verified and all foals with=20
HYPP bloodlines will be tested for HYPP.=20
Source: _AQHA Update_, "Rules Changes for 1997" Spring 1996
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