Hyperkalemic periodic paralysis
), also known as Impressive Syndrome
, is an inherited autosomal dominant
disorder which affects sodium channels
cells and the ability to regulate potassium
levels in the blood
. It is most commonly associated with horses
, but also occurs in humans
, where it is also called Gamstorp episodic adynamy
Disease in horses
Symptoms and presentation
This inherited disease is characterized by violent but not dangerous muscle twitching
and substantial muscle weakness
among affected horses. HYPP is a dominant genetic
disorder; therefore heterozygotes
bred to genotypically
normal horses have a statistic probability of producing clinically affected offspring 50% of the time.
Horses affected with HYPP or twitching syndrom cannot be treated with some possibility of reducing symptoms, but the degree that medical treatment helps varies from horse to horse. Therefore, horses with HYPP should only be ridden by experienced riders, if anyone, because episodes of paralysis can come on very suddenly and a rider has to be extremely alert to recognize an impending episode which may cause the horse to lose control of its body.
Some horses are more affected by the disease than others and some attacks will be more severe than others, even in the same horse. SYmptoms of an HYPP attack include:
-Prolapse of the third eyelid - this means that you may note the third eyelid flickering across the eye, or covering more of the eye than normal
-Weakness in the hind end - the horse may look as though it is 'dog-sitting'
-Abnormal whinny - this is because the muscles of the voicebox are affected as well as other muscles
-Death - In a severe attack the diaphragm is also paralysed and the horse can suffocate to death.
HYPP attacks do not occure randomly they are patterned and can strike a horse standing calmly in his box just as easily as during exercise. Following an HYPP attack the horse appears normal and is not in any pain which helps to distinguish it from Tying Up Sundrome. Horses with Tying Up Syndrome usually suffer attacks in connection with exercise and the attack can last several days. Because muscle tissue is actualy damaged in an attack of Tying Up Syndrome the horse will be in pain during and following an attack. A blood test will reveal elevations in certain muscle enzymes after an episode of Tying Up and so the two diseases, while superficially similar are easily distinguished from one another.
Unlike with seizures, horses with HYPP are not fully conscious and lucid during an attack. Horses which suffocate to death during an HYPP attack die. Horses which colapse during an episode are also clearly distressed as they repeatedly struggle to get to their feet again.
Inheritance and prevalence
The disease is linked to the bloodline of the famous American Quarter Horse
, who has over 55,000 living descendants as of 2003
. Although the disease is primarily limited to the American Quarter Horse breed and closely related breeds such as American Paint Horses
at this time, cross-breeding has begun to extend it to crossbreds
recognized by other breed registries
as well as grade horses
. The spread of the disease is perpetuated by the favorable placings given to affected horses in halter
competition at horse shows
, because a secondary charactistic associated with N/H and H/H horses is heavy, bulky muscling that is favored by stock horse
judges, a trend that began with Impressive and predates the modern understanding of the disease.
In 1994, researchers at the University of Pittsburgh
, with a grant from various horse organizations, isolated the genetic mutation responsible for the problem and developed a blood test
for it. Using this test, horses may be identified as:
- H/H, meaning they have the mutation and it is homozygous. These horses always pass on the disease.
- N/H, meaning they have the mutation and it is heterozygous. These horses are affected to a lesser degree, and pass on the disease 50% of the time.
- N/N, meaning they do not have the mutation and cannot pass it on, even if they are descendants of Impressive.
Recently, horse organizations have begun instituting rules to attempt to eliminate this widespread disease. The American Quarter Horse Association
(AQHA) now mandates testing for the "Impressive" mutation and will no longer register homozygous
(H/H) foals as of 2007
, with discussion of heterozygous
(N/H) foals pending. The Appaloosa Horse Club
(ApHC) will no longer accept homozygous foals as of 2008
. It is believed that both primary palomino
registries will exclude any foal carrying the "Impressive" mutation as of 2007
. The main organization affected by HYPP that has not yet taken action is the American Paint Horse Association
(APHA), although many other smaller organizations are also affected.
Disease in humans
Although much rarer, hyperkalemic periodic paralysis has also been observed in humans. In humans the disorder causes episodes of extreme muscle weakness, attacks beginning in infanthood and depending on the type and severity of the HYPP it can will increase or stabilize until the fourth or fifth decade where attacks can decline and can altogether stop or, depending on the type, continue on into old age. Factors that can trigger attacks include rest after exercise, potassium-rich foods, stress, fatigue, weather changes, certain pollutants (eg: Cigarette smoke) and periods of fasting. Muscle strength improves between attacks, although many affected people may have increasing bouts of muscle weakness as time goes on (abortive attacks). Sometimes with HYPP those affected may experience degrees of muscle stiffness and spasms (myotonia) in the affected muscles. This can be caused by the same things that trigger the paralysis, dependent on the type of myotonia. (See also paramyotonia).
Some people with hyperkalemic periodic paralysis have increased levels of potassium in their blood (hyperkalemia) during attacks. In other cases, attacks are associated with normal blood potassium levels (normokalemia). Ingesting potassium can trigger attacks in affected individuals, even if blood potassium levels do not go up.
The most common underlying cause is one of several possible point mutations in the gene SCN4A. The SCN4A gene provides instructions for making a protein that plays an essential role in muscles used for movement (skeletal muscles). For the body to move normally, these muscles must tense (contract) and relax in a coordinated way. Muscle contractions are triggered by the flow of certain positively charged atoms (ions), including sodium, into muscle cells. The SCN4A protein forms channels that control the flow of sodium ions into these cells. Mutations in the SCN4A gene alter the usual structure and function of sodium channels. The altered channels cannot properly regulate the flow of sodium ions into muscle cells, which reduces the ability of skeletal muscles to contract. Because muscle contraction is needed for movement, a disruption in normal ion transport leads to episodes of muscle weakness or paralysis.
This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.
- National Library of Medicine. Hyperkalemic periodic paralysis
- Tufts University: Cummings School of Veterinary Medicine. http://www.tufts.edu/vet/sports/hypp.html#3