Hyperkalemic periodic paralysis (HYPP) is a muscle disorder of the horse that causes episodes of paralysis or muscle weakness. The condition is caused by a genetic defect affecting muscles cells (e.g., their ability to transport sodium ions across cell membranes).¹ This interferes with the horse’s ability to contract normally in response to electrical nerve signals resulting in muscle spasms and weakness. As a result, horses experience spontaneous episodes of muscle tremors, weakness, paralysis and collapse, sometimes accompanied by respiratory distress.

HYPP has been traced back to one horse named Impressive and also carries the alternative name, Impressive Syndrome.²This condition is not to be confused with mountain sickness or other intermittent maladies of the horse which have other unrelated causes. Environmental factors however, may increase the likelihood of a paralysis episode (e.g., high altitudes, exposure to cold, stress, high-potassium diets, fasting, anesthesia or heavy sedation).

Episodes of HYPP

As indicated above, horses with HYPP experience episodes of muscle spasms, weakness or paralysis. During episodes, horses often have shortness of breath and respiratory distress due to the paralysis of upper respiratory muscles. 

HYPP is a dominant disorder, meaning that both homozygous positive (HH) and heterozygous (nH) horses are affected. Only homozygous negative (nn) horses are not affected. Because HYPP is dominant disorder, its effects can also occur in other breeds of horses when intermixing occurs.³ This makes the recognition of this disorder very important in preserving breeding integrity horses.

Horses with two copies of the mutated gene (i.e., they are homozygous for the mutated gene) are affected more severely, with more frequent episodes of weakness or paralysis and more severe signs of upper airway obstruction.¹ In severe occurrences, a horse may die suddenly during severe episodes due to asphyxiation or heart failure. Emergency treatment may be required during attacks, and in severe cases of respiratory distress, horses may require a tracheotomy.³

Horses only need one copy of the mutated gene to be affected, however. HYPP occurs in the following horse breeds:

• Quarter Horses
• American Paint Horses
• Appaloosas
• Quarter Horse crossbreeds

Clinical signs of hyperkalemic periodic paralysis are usually first observed in young horses of two to three years of age. After that, horses will experience paralytic episodes throughout their lives. Episodes are usually brief and usually last for between 15 to 60 minutes.² Thus, early episodes are frequently overlooked by their owners.

HYPP: Scope and Diagnosing

In a study of 978 Quarter horses between 1989 and 1991, it was found that 43 horses (4.4%) had the gene mutation responsible for HYPP and all affected horses were traced back to the single ancestral sire (Impressive). Hyperkalemic periodic paralysis affects males and females equally, and with equal frequency.²

The most sensitive test for HYPP is the DNA test for hyperkalemic periodic paralysis–type sodium channel mutation. The test can detect homozygous (two copies of the mutation) and heterozygous (one copy of the mutation) affected horses, as well as non-affected (no gene mutation) horses.² A definitive diagnosis can also be made based on clinical signs, together with elevated blood potassium levels, although potassium levels in the blood may not always be outside of the normal range. Mandatory testing for HYPP was introduced by the American Quarter Horse Association in 1996, and homozygous affected horses are ineligible for breeding.¹ Breeding from two heterozygous affected horses will also produce affected offspring, which should be avoided whenever possible.

Acetazolamide for Horses With HYPP

Acetazolamide is typically used to treat metabolic alkalosis or glaucoma in dogs and cats and hyperkalemic periodic paralysis (HYPP) in horses. It is a white to faintly yellowish-white, crystalline, odorless powder that is weakly acidic.⁴Acetazolamide is supplied as a sterile powder, requiring reconstitution for intravenous use, as a bulk solution, and as capsules and tablets. 

It is useful in the treatment of certain dysfunctions of the central nervous system that may lead to attacks of paralysis and muscle weakness, as well as HYPP in the horse.⁴

Acetazolamide acts as a potent carbonic anhydrase inhibitor that is effective in control of fluid secretion. In the eye, this inhibitory action decreases the secretion of aqueous humor and results in a drop in intraocular pressure, making it useful in treatment of glaucoma in horses.⁴ Acetazolamide has been found to be more effective than hydrochlorothiazide in controlling clinical signs of HYPP.⁴ It is also effective as a diuretic in cases of abnormal fluid retention. The diuretic effect of acetazolamide is due to its action in the kidney, resulting in renal loss of sodium, water, and potassium, leading to alkalinization of urine and promotion of diuresis in horses. Acetazolamide is also used as an adjunctive treatment of edema due to congestive heart failure.⁴

Where to buy Acetazolamide 

Acetazolamide is available in the U.S. through several pharmaceutical manufacturers and through veterinary custom compounding companies. 

Please consult a licensed veterinarian prior to beginning any treatment regimen.

FOR RX ONLY: A valid prescription from a licensed veterinarian is required for dispensing this medication.

¹Zeilmann M. HYPP--Hyperkalemic Periodic Paralysis in Horses. Tierarztl Prax. 1993 Dec; 21(6):524-7. German. PMID: 8122239.

²Steiss, J. E., & Naylor, J. M. (1986). Episodic Muscle Tremors in a Quarter Horse: Resemblance to Hyperkalemic Periodic Paralysis. Canadian Veterinary Journal, 27(9), 332-335.

³Spier, S. J., Carlson, G. P., Holliday, T. A., Cardinet III, G. H., & Pickar, J. G. (1990). Hyperkalemic periodic paralysis in horses. Journal of the American Veterinary Medical Association, 197(8), 1009-1017.

⁴equimed.com.