HYPP - Still With Us
A recent journal article not only spoke about hyperkalemic
periodic paralysis (HYPP) as a finding in adult Quarter
horses, but also recently implicated it as a differential
in foal deaths as well. Why?
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 usually highly rated when
shown in halter classes in the show ring. This condition
has no sex predilection, although it is mostly seen in males,
and no breed restrictions. The disease is very similar to
one known to exist in humans called adynamicaepisodicahereditaria
or hyperkalemic periodic paralysis (HPP). In horses, lineage
of affected individuals has been traced back to a single
sire.Impressive, known for his greatness in halter showing.
Over 50,000 registered Quarter horses are related to known
carriers of this disease. This disease has been shown to
be genetically transmitted as an autosomal dominant trait.
This also means that the heterozygotes have the potential
to manifest HYPP as well. However, those offspring that
are homozygotes tend to be more severely affected.
HYPP is commonly characterized by signs such as muscle
spasm, weakness, recumbency, and high serum potassium concentrations.
Research shows that these signs are a result of a permanent
defect in ion transport across the skeletal muscle cell
membrane, resulting in increased sodium permeability, reduced
polarization, and thus changes in muscle excitability. Its
association with certain alleles of the gene coding for
skeletal muscle sodium channels has led researchers to believe
that a point mutation results in a single amino acid in
the alpha subunit of the sodium channel protein. Normal
channels close once the muscle membrane has depolarized.
Defective channels remain open and allow excessive influx
of sodium resulting in greater efflux of potassium, and
continuous membrane depolarization. In severe attacks, weakness
can be seen due to the abolition of membrane action potentials.
The hyperkalemia that is seen is secondary to the influx
of sodium, and the release of muscle potassium as potassium
channels open to repolarize the membrane.
Factors that may trigger clinical attacks can be attributed
to a variety of conditions such as chilling, transportation,
recovery from anesthesia, or any stressful event such as
showing. HYPP has been misinterpreted as a wide variety
of other diseases, such as colic, "tying-up" syndrome,
and recumbency for one reason or another. The earliest clinical
signs of muscle fasciculations can progress to muscle group
spasms, retraction of the lips and eyelids (risussardonicus),
stiff jaw, prolapse of the tired eyelid, increased respiratory
rate, inspiratorystridor, and stiff gait in more severe
cases. Whether standing or recumbent, most horses will sweat
profusely during an episode. Horses have been known to die
during an attack from respiratory paralysis, or cardiac
failure secondary to hyperkalemia. Horses usually appear
normal after an attack, whereas horses with "tying-up"
syndrome walk with a stiff gait and have painful, firm muscles
of the hindlimbs, rump or back. HYPP is also not usually
associated with exercise, but seen at rest, during feeding
or following stressful events.
Testing for HYPP can be done in several ways. In the field,
the test of choice is the gene probe for HYPP-type sodium
channel DNA. This is the most sensitive test for detecting
the mutation in susceptible horses, and requires
whole anticoagulated(EDTA) blood. Diagnosis can also be
made based on clinical signs of HYPP together with an elevated
serum potassium concentration. To avoid problems with potential
potassium leakage due to leakage from red blood cells, one
should separate plasma soon after the blood has clotted.
Testing with electromyography, which measures the electrical
activity present in selected muscles, can also be done to
further support a diagnosis. When necropsies are performed,
tissues can be used for both gene probe testing, as well
as histopathological interpretation. Histologically, one
can see vacuolization in type 2B muscle fibers with mild
degenerative changes. Electron microscopy shows dilatations
of the sarcoplasmicreticulum of myofibers. Diagnosis based
on genetic testing of whole blood is particularly useful
in prepurchaseexams, and in deciding whether or not to use
a particular horse for breeding.
Recently, four foals presented to clinics were reported
to have episodes of upper airway stridor while being restrained
for physical examination. Endoscopic examination revealed
laryngeal spasms and partial pharyngeal paresis in each
one. Electromyography showed abnormal muscle activity
in the foals as well as their dams. Two of the foals had
to have emergency tracheostomiesperformed to restore an
airway after it collapsed due to the over-excitement. On
the basis of clinical signs, electromyographic interpretation,
response to treatment, and increased serum potassium levels,
a diagnosis ofHYPP was made in each case. For this reason,
HYPP should be considered as a differential diagnosis for
upper airway stridor, and/or sudden death possibly due to
asphyxiation attributable to laryngeal collapse.
This disease has been recognized for several years now,
but its importance is changing from one of scarcity, to
one of diversity, from one of novelty, to one of an important
genetic disease. Without prompt action, the breeding of
affected individuals will greatly increase the expression
of this serious disease. Veterinarians can help prevent
this from happening by testing suspect horses and educating
the public about this condition.
-Kevin R.Cawood, Class of 1996
-Edited by JaniceSojka,DVM