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Hyperkalemic Periodic

Paralysis in Horses

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Hyperkalemic periodic paralysis (HYPP) is a muscular disease that
affects both horses and humans. It is caused by a hereditary
genetic mutation that disrupts a protein called a sodium ion
channel, a tiny gateway in the membrane of muscle cells. The
mutation affects the channel's normal opening and closing, such
that uncontrolled sodium influxes occur. These influxes in turn
change the voltage potential of muscle cells, causing
uncontrolled muscle twitching or profound muscle weakness. High
levels of potassium in the blood usually are present when the
disruptions in the ion channel occur.

What are effects of HYPP?

Horses with HYPP can experience unpredictable attacks of
paralysis which, in severe cases, can lead to collapse and sudden
death. The cause of death usually is cardiac arrest and/or
respiratory failure. The disease is characterized by intermittent
episodes of muscle tremors manifested by generalized or localized
shaking, trembling and weakness. Occasionally, episodes are
accompanied by respiratory noises resulting from paralysis of the
muscles of the upper airway.

What is the origin of the genetic mutation causing HYPP?

The original genetic mutation causing HYPP was a natural mutation
that occurred as part of the evolutionary process. The majority
of such mutations, which are constantly occurring, are not
compatible with survival. However, the genetic mutation causing
HYPP produced a functional, yet altered, sodium ion channel. This
gene mutation is not a product of inbreeding.

The gene mutation causing HYPP inadvertently became widespread
when breeders sought to produce horses with heavy musculature,
but this does not mean that all horses with well developed
musculature possess the disease.

The mutant gene causing HYPP presently has been
identified in the descendants of the horse "Impressive". The
American Quarter Horse Association has more than 102,000
descendants of "Impressive", the American Paint Horse Association
and the Appaloosa Horse Club also have registered a substantial
number of impressive-bred horses, but have no precise figure.

In a recent study (Naylor et al, 1992. J. Am. Vet. Med. Assoc.,
3:340-343), it was found that over 50,000 registered Quarter
Horses are positive for HYPP. Thus, the disease may be
widespread, and many of the most successful show horses may be
HYPP positive.

What are the chances of a positive horse producing a positive

If a horse carrying one copy of the mutant gene - a heterozygote
- is mated with an unaffected horse, there's a 50 percent chance
that the foal will have HYPP. If the horse carries two copies of
the mutant gene - a homozygote - all offspring will be
HYPP-positive, regardless of the other parent. If two
heterozygotes are mated, there's a 75 percent chance that the
foal will be affected. Two unaffected horses cannot produce a
positive foal. Homozygous horses are affected more severely than
heterozygous horses. Under ideal management practices, a mutant
gene does not appear to have adverse effects, but stress and/or
increased potassium in the serum can trigger clinical signs of
muscle dysfunction.

How is HYPP diagnosed?

The best way to determine whether a horse is HYPP positive is a
DNA test. The identification of this gene mutation is the basis
for the DNA test used to diagnose HYPP. There is no cure for
HYPP, but a consistent diet and regular exercise may minimize the
risk of attack.

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