Monday, April 8, 2013

Hyperkalemic Periodic Paralysis

"I was given a new English saddle for Christmas and raced up to the barn to try it on "Mister".  It fit great, we rode around, I played with him, groomed him, gave him his grain, and put him away.  He was found dead in his stall the next morning, and the vet said he died about 12 hours earlier, which was about 2 hours after I put him away Christmas day.  I was devastated."-Tami

The story of Tami is that of terror and sadly the truth for up to 25% of the Quarter Horse owner population.  Right now you are asking, "What was the cause of death?" Well the answer would be Hyperkalaemic Periodic Paralysis, or HYPP a genetic mutation with in the cell membrane of muscle fibers.  HYPP usually first appears within the first 10 years of life with attacks of muscle weakness caused by cold, rest after exercise, fasting, or ingestion of potassium (Fontaine, 1000).  This muscle disease is that of genetic defect, more specifically a point mutation, in the DNA of the Sodium Channel Gene.  The mutation is an Autosomal Dominant Trait, which means only one copy of the gene is needed to express HYPP, and it is also equally occurring in males and females.

Here is a Handy Glossary to Help Understand HYPP

Pedigree of HYPP Breeding
Where did this mutation originate? Well the story is rather Impressive.  Over 20 years ago, a horse named Impressive was winning all the halter classes. Impressive was well named - he was so strikingly muscled that he never lost a halter class. It is became easy to understand why Impressive was in huge demand as a breeding stallion. Impressive showed that he had a very important trait as a breeding stallion - he had the ability to pass on his wonderfully sculptured musculature to his offspring. It was not for quite some years that people started noticing that Impressive's offspring had inherited more than just his looks. For the gift of Impressive's massive muscles came with a far less welcome inheritance - which came in the form of intermittent episodes of weakness, collapse, or even death from the mutation causing HYPP.

Point Mutation
According to AAEP (American Association of Equine Practitioners), the mutation is a point mutation.  A point mutation is a mutation where one letter, or point, in the DNA is changed and in this case changes the coding of the gene.  The new mutated gene codes for an abnormal channel to be expressed in the skeletal muscles.  Sodium channels are "pores" in the muscle cell membranes, which control concentrations of potassium and sodium ions in the muscle fibers.  When the defective gene is present, it causes that channel to become "leaky".  This allows the potassium ions to leak, which then, overexcites the muscles causing them to contract involuntarily.  

Horse During HYPP Attack

"Hyperkalaemic periodic paralysis results in a phenylalanine–leucine substitution at the voltage-dependent skeletal muscle. Sodium channels are usually closed in resting muscle but are triggered to open as the membrane potential moves toward threshold. The resultant rapid increase of sodium leads to membrane depolarization, giving rise to the early phase of the cell action potential. Once the membrane is fully depolarized the sodium channels close and the potassium channels open, potassium leaves the cell leading to cell repolarization.  In HYPP horses the sodium channels remain open following membrane depolarization resulting in a permanent reduction of membrane potential causing involuntary muscle contraction, followed by fatigue and weakness"(Secombe, Lester).

In the video to the left, this horse Dillon has been tested for HYPP and his results were negative.  As you can see, he is having an attack to some degree.  While the test is generally effective, it cannot prove a horse to be negative.  When reading the comments under the video on YouTube, the owner explains what seems to have sent Dillon into the HYPP attack.  The owner explains how he worked him then gave him alfalfa hay afterwards.  Alfalfa is very high in potassium, which could have been what triggered his attack.  A proper diet can keep symptoms at bay.

A suggested diet to manage a horse with HYPP would be a diet low in potassium, along with feeding multiple times a day, and frequent exercise and/or allowing the horse access to a large field.. Low potassium feeds include a late boom Timothy or low potassium grass hay, beet pulp with no molasses, and small amounts of oats.  This high glucose, high carbohydrate diet allows the pancreas to be stimulated to secrete insulin which lowers glucose levels and potassium levels.  There are also medications that can be prescribed by a veterinarian that help stabilize blood levels and that increase renal potassium ATPase activity. The medications will help rid the body of potassium and help with fluctuations of the potassium ion levels in the blood which can trigger an attack.

An attack can be a scary encounter.  A DNA test has been formulated by University of California Davis.  The test requires the collection of hairs including the hair's roots.  When analyzing the hair, the test looks the specific genetic mutation associated with HYPP, which we know is associated with those as descendants of "Impressive".  As required by the American Quarter Horse Association in 2006, rule 205 states:  "all horses that are to be registered to the AQHA (American Quarter Horse Association) must be tested for HYPP.  The horses must test negative to become registered."

The problem then becomes, people do not want to know if their horse has HYPP and people do not want to tell potential buyers the horse has the possibility of being HYPP positive.  However, legally, a person has the right to know!  The Sale of Goods Act of 1979 Sections 13 & 14 cover the sale of horses.  Both sections deal with the private and public sale of a horse.  Under both sections, claims can be filed for the "misrepresentation" of the horse.  This would include a false claim that the horse is negative for HYPP.

 A Pre-Purchase Exam performed by your vet, is always suggested when purchasing a horse.  The exam should allow you to gain a general understanding of the horse's health.  From the health of the horse's teeth to x-rays to a complete lameness exam and as far as drug testing can be included in this exam.  Of course, if there were the question that the horse could be an "Impressive" descendant a test for HYPP would not be out of the question for this exam either.  In any event, that the horse comes back positive for HYPP or any other sort of alarming results appear upon the pre-purchase exam, one would be advised not to pursue any further testing on horse by the vet.

The story of Hyperkalaemic Periodic Paralysis is rather Impressive.  This gene mutation causes an unbelievable and majestic musculature in the descendants of Impressive, the mutation also formed a devastating disease.  People are breeding to Impressive descendants for this glorious musculature to win halter classes, but ignoring the severe disease that has no cure.  Impressive's offspring have naturally fit bodies.  While ideally we could keep breeding Impressive descendants because, who would not want a perfectly muscled dream horse?  However, these dream-like genes also carry a nightmare of episodes of weakness, collapse, or even death from the mutation forming HYPP.  Working horses regularly will provide a beautifully toned horse and can lead to the winning of a halter class.  Along with the win of the halter class, the hard work put in by the horse and handler will create a bond worth more than a blue ribbon.

Works Cited
Cristy J. Secombe, Guy D. Lester
           The role of diet in the prevention and management of several equine diseases ☆
           Animal Feed Science and Technology, Volume 173, Issues 1–2, 20 April 2012, Pages 86–101.

Hyperkalemic Periodic Paralysis and the Adult Muscle Sodium Channel α-Subuit Gene
           Bertrand Fontaine, Tejvir S. Khurana, Eric P. Hoffman, Gail A. P. Bruns, Jonathan L.
           Haines, James A. Trofatter, Mark P. Hanson, Jaimie Rich, Heather McFarlane, Diane   
           McKenna Yasek, Donna Romano, James F. Gusella and Robert H. Brown Jr.
           Science , New Series, Vol. 250, No. 4983 (Nov. 16, 1990), pp. 1000-1002