Registry Services - Genetic Disorders

HYPP (Hyperkalaemic Periodic Paralysis)

Please note:
HYPP kits can be obtained by contacting the AQHA office. The HYPP kit costs $60 and can be purchased from AQHA.

Progeny of HYPP positive parents (N/H) must be tested using the official procedure before they will be considered for registration in either the Stud Book or Appendix Registers.

From 1 August 2006 any horse that tests positive for HYPP (N/H) will not be considered eligible for registration into the Stud Book or Appendix Register until they are spayed or gelded.  For more information, please contact the office.

Imported horses or horses applying to be registered for Imported Semen, that do carry the IMPRESSIVE lineage, must produce the official results of a HYPP test or if not contact AQHA for a testing kit.

Imported horses testing positive (N/H) or (H/H) will not be accepted into the Sud Book or Appendix Registers of the Association.

 

What is HYPP?
By Andrew Dart; BVSc, DVCS, Diplomate of the American College of Veterinary Surgeons.

Hyperkalaemic Periodic Paralysis is a genetic disease, identified in some lines of horses, that affects the muscular system. The muscle cells of horses afflicted with HYPP have a defect in a protein system called the sodium ion channel. The sodium ion channel is a tiny gateway in the cell membrane that forms a selective pathway for charged electrolytes communicating between the outside and the inside of the cell. In normal horses the sodium ion channel is involved in maintaining a balanced electrical charge across the muscle cell membrane. It is an alteration in this electrical charge that is responsible for the normal contractile activity of muscles. In horses afflicted with HYPP the defect in the sodium ion channel permits periodic, uncontrolled influxes of sodium, a positively charged electrolyte into the cell thereby altering the electrical balance across the muscle cell membrane and leading to unpredictable and uncontrolled periods of muscle activity.

What is the origin of this defect?
The origin of the defective sodium ion channel has been traced back to a genetic mutation. Genes are responsible for determining the individuality, structure and function of every living being. Each individual has many genes, which are stored collectively as DNA in every cell within the body. There are two identical DNA molecules in each cell and therefore there are two identical sets of genes, one on each of the two DNA molecules. In horses with HYPP one or both of the genes that determine the structure and function of the sodium ion channel have been altered by a natural mutation, which has rendered the pathway defective. Mutations are part of the natural evolutionary process to select for lines of animals that are better suited to their ever changing environment. Most mutations are not compatible with life however the mutation responsible for HYPP is unusual in that-it has led to an altered yet functional sodium ion channel.
Recent breeding trials have identified HYPP as an autosomal dominate trait. This means that it can affect males equally as frequently as females. Because it is a dominate trait even if only one of the gene pair has mutated, clinical signs of the disease can be manifested. This has led to the recently adopted terminology in the literature that horses are either NH (1 normal and 1 HYPP gene) or HH (both HYPP genes). More correctly these are referred to as heterozygous (NH) or homozygous (HH) gene pairs.

What are the clinical signs of HYPP?
The clinical signs associated with HYPP vary widely among different horses, with some affected horses never demonstrating any signs while others have all the classical manifestations. However, it does appear that horses that have homozygous gene pairing (HH) are more severely affected than horses with a heterozygous (NH) gene pairing. The reason for different horses showing variable clinical signs is not well understood and is presently under investigation. However, it is important to realise that horses with the gene mutation characteristic of HYPP that show no clinical signs are able to pass the mutation onto their offspring as effectively as horses that show severe clinical signs. Horses with HYPP often show muscle tremors and fasciculations, and may make a respiratory noise during attacks. These signs may become severe enough to lead to muscle weakness and cause the horse to lie down or collapse. During these episodes horses usually appear bright and alert although they may appear anxious. Recumbent horses are unable to rise even when coaxed. Invariably recumbent horses will spontaneously rise within 30 to 60 minutes although there are reports of horses remaining down for up to 7 hours. Characteristically blood potassium concentrations rise sharply during the period of time horses are showing clinical signs. In between episodes, horses afflicted with HYPP appear to be normal and have blood potassium concentrations within normal limits. Horses with HYPP can die suddenly from respiratory or cardiac arrest however this is uncommon and it is important to realise that there are far more common causes of sudden death. Stressful situations such as transport, changes in management practices or environment, strenuous training, or sudden changes in diet can precipitate attacks. Similarly elevated blood potassium levels secondary to diets high in potassium can initiate an attack. Molasses, a common component of sweet feeds and lucerne hay, are rich in potassium. Oat hay and raw grains such as oats, barley and corn have a low potassium content. Diets consisting of oat hay or half oat hay and half lucerne hay with or without grain have reportedly controlled clinical manifestations of this disease in affected horses. Horses with HYPP do not "grow out of" this disease. However clinical signs seldom become apparent prior to weaning and may become less severe with increasing age. This may be related to the variable effects of stress on different age groups of horses.
It is essential to realise that the clinical signs manifested by horses with HYPP are very similar to far more common conditions such as colic, tying up, neurological conditions, dehydration and shivers. Not every horse that shows muscle tremors or is recumbent has HYPP. At this point in time studies - are being undertaken to try and determine the true incidence of horses with HYPP, and how many of these horses actually manifest clinical signs. It is likely that the incidence of the disease in Australia is going to be lower than in America and given that, it should be more readily managed.

How is this disease diagnosed and how do I get my horse tested?
Originally a potassium challenge test was used to diagnose this condition in suspect horses. This involved stomach drenching these horses with a potassium rich solution to raise blood potassium, in an attempt to precipitate clinical signs.
More recently a blood or hair test has been developed whereby the specific gene sequence determining the function of the sodium ion channel on the two DNA molecules are examined for the presence of the mutation. This test does accurately and reliably determine whether the horse has the gene mutation and whether the mutation is heterozygous (NH) or homozygous (HH).

Which horses should be tested?
HYPP is the first genetic disease that has been identified using a relatively new science called Molecular Genetics. Using this science, specific genes on the DNA molecules within body cells are selected and examined. Until further studies looking at gene sequences other than those presently being examined are performed the full impact of this and other genetic diseases will not be entirely known. At this point in time the genetic mutation causing this specific defect in the sodium ion -channel has been traced back to the sire "Impressive". It is possible that the mutation goes back beyond "Impressive". Further research is underway to try and determine the specific origin. Because HYPP is a genetic disease, any descendant of "Impressive" could have inherited the gene mutation. So at this point in time certainly any owner of a horse with "Impressive" in its bloodline and who is concerned about HYPP from a diagnostic, treatment or breeding purpose should investigate having that horse tested.
It is important to realise that while "Impressive" is a popular sire of Quarter horses he and his descendants have also been very popular crossbreeding with other breeds of horses and with horses used for other equestrian disciplines. All horses, irrespective of breed or use with "Impressive" in their bloodline are equally at risk to inherit the HYPP genes.
Further research is underway to determine whether other breeds or lines of horses have this mutation or a similar mutation at another site on the DNA molecule that has yet not been identified. Until this research is completed it is impossible to know whether this condition is specific for the "Impressive" bloodline or for that matter the Quarter horse breed.


Is there any treatment for horses with HYPP?
Horses with HYPP rarely die suddenly and information on effective preventative and emergency treatment is available. Dietary management includes feeding a diet low in potassium and feeding on a regular basis. Horses appear to do better if they are not stabled or only stabled at night. A regular exercise and management program will minimise stress.
Reports of the daily use of acetazolamide, a diuretic, have been mentioned and recommended. Diuretics are a group of drugs that increase urine output and have the potential to dehydrate horses particularly if they are not good drinkers or are in heavy work. Acetazolamide also increases the excretion of potassium from the body in the urine. Because body stores of potassium are minimal it can lead to depletion of potassium and result in the clinical manifestations of hypokalaemia (low blood potassium). The indiscriminate use of acetazolamide should not be recommended. Horses suffering from an acute attack often recover spontaneously, however in severe cases where the horse is recumbent or suffering from respiratory distress, immediate veterinary attention is warranted. Treatment with intravenous fluids such as 5% dextrose with added calcium gluconate will help stabilise muscle membranes and lower blood potassium. Most horses will respond immediately to this form of treatment.

What are the implications of HYPP on the industry?
Many reports have highlighted that horses with HYPP can live healthy and productive lives, giving their owners many hours of pleasure. Indeed it appears that, at the least, some horses that have positive DNA tests have reportedly never demonstrated clinical signs. However on the other hand, it is also possible that a horse with this condition could unpredictably collapse during work, injuring the rider. While it could be argued that this is unlikely and could happen unpredictably under other circumstances, it would be irresponsible for a third party to know of the condition and for the rider to be uninformed. There have also been many reports comparing HYPP with other common ailments such as colic and tying up. However, I believe this is not a reasonable comparison, in that we know HYPP to be a heritable condition resulting from a specific genetic mutation that, granted, may be compatible with life, but is an undesirable autosomal dominant trait, passed on by identifiable carriers. This makes HYPP a unique disease in the horse that needs to be considered from a different perspective.
The horse industry can make only one of two decisions regarding this disease. It can choose to ignore the problem or aim to eventually decrease the incidence of the mutant genes in the horse population into extinction by selective breeding. I think there would be little argument that the majority, if not all parties, would prefer to eradicate the disease.
It is the approach to this eradication that is the sensitive topic. It is not for me or any other individual to make that decision. Hopefully educated decisions can be made that consider both the individual and the best interests of the horse industry and, more specifically, at this point in time the Quarter Horse industry and the "Impressive" line of horses. This condition is unusually widespread geographically because of the popularity of "lmpressive" as a sire. This popularity arose from the many champion qualities and the many more they have inherited from the other side of their pedigree. It is important to keep in perspective that HYPP is only one trait. It would be foolish for the horse industry to condemn "Impressive" and his descendents based on this one trait and lose the many others with it. We are lucky in that we have the knowledge and ability to selectively eradicate this trait, while preserving the many other great qualities this line of horses have given the industry.

How do we go about eradicating HYPP?
There are many figures thrown about regarding the percentage of affected offspring that will be produced from the mating of affected parents. To understand these figures one must have some understanding of genetics. All cells within the body of all horses have two sets of genes. Because the offspring of all matings must have two sets of genes, each parent can only donate one set each to the developing embryo. Therefore, each sperm and each egg only has one of the parent's original gene pair. This means that 100% of the eggs or sperm from a homozygous (HH) mare or stallion will carry a mutant gene (H). Therefore any mating where one of the parents is homozygous (HH) will perpetuate the mutant gene in the population irrespective of whether the other parent is normal (NN) or affected (NH or HH). Homozygous horses are undesirable in the population as breeding animals. If homozygous horses are not used as breeding stock this leaves horses that are heterozygous (NH) and normal horses (NN) as eligible breeding animals. It is important to realise that breeding two normal horses always produce 100% normal offspring. Breeding two heterozygous (NH) together or 1 heterozygous horse to a normal horse can produce affected offspring, and will perpetuate the gene in the population. However more importantly, these matings can also produce foals that do not carry the mutant gene that are potential breeding stock.
To put this in context with the previous discussion, mating heterozygous horses to normal or other heterozygous horses can produce a foal without the disease (NN) but with the characteristics and features of the "Impressive" line that have the potential to make that foal a champion and excellent breeding stock. However these matings can also produce champions with the mutant genes. If our aim is to eradicate the mutant gene from the horse population then only those foals born without the mutant gene should be used as breeding animals.
In essence this suggests we should not use the existing or future homozygous (HH) horses in the breeding pool. Existing heterozygous (NH) horses can still be used for breeding to maintain all the desirable features of existing champion sires and dams. However we should only select those foals from these matings that are negative for the disease (NN) for future breeding. This will dilute the mutant gene to extinction without losing many champion qualities of the "Impressive" line and without economically crippling the individual or the industry.
Using this concept a policy could be easily implemented and policed by the various horse societies, specifically the AQHA whereby the ultimate decision of which direction the individual horse owner or breeder wishes to take remains in their hands, but keeps the best interests of the entire industry in mind.

What are the chances of getting a normal foal from a specific mating?
It is important to understand that all these figures are educated guesses. Each heterozygous (NH) horse produces approximately 50% normal (N) and 50% affected (H) sperm or eggs. Fertilization is a random event. That means that any combination of sperm and egg may meet after mating. The chance that an affected foal may come from a mating between two heterozygous horses is greater than from a heterozygous horse with a normal horse purely because there are more mutant genes available.
More specifically the chances are that three out of four foals produced by mating two heterozygous horses together are likely to be affected while two out of four foals produced by mating a heterozygous horse with a normal horse are likely to be affected. However, as noted, fertilization is a random event and it is also possible that all foals from these matings may be unaffected. So while breeding an affected horse-does assume some risk of producing an affected foal, that risk may be worthwhile if the particular features the individual breeder is looking for are present in that particular parent. In summary it is important to put HYPP into perspective and to seek educated advice to understand the condition and it's implications before condemning the affected population to the detriment of the industry.

 

By Andrew Dart; BVSc, DVCS, Diplomate of the American College of Veterinary Surgeons.

 

 

 

Australian Quarter Horse Association
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