Hyperkalemic Periodic Paralysis

Hyperkalemic periodic paralysis (HyPP) is an autosomal dominant trait affecting Quarter Horses, American Paint horses, Appaloosas, and Quarter Horse crossbreeds worldwide. A point mutation that results in a phenylalanine/leucine substitution in the voltage-dependent skeletal muscle sodium channel a subunit is responsible. The prevalence in Quarter Horses is ~4%.

Clinical signs range from asymptomatic to intermittent muscle fasciculations and weakness and are first identified from foals to 3 yr of age. Homozygous horses are often more severely affected and may be identified at a younger age than heterozygotes. A brief period of myotonia is often observed initially, with some horses showing prolapse of the third eyelid. Muscle fasciculations beginning on the flanks, neck, and shoulders may become more generalized. While most horses remain standing during mild attacks, weakness with swaying, staggering, dogsitting, or recumbency may be seen, with severe attacks lasting 15-60 min or longer. Heart and respiratory rates may be elevated, but horses remain relatively bright and alert. Respiratory distress occurs in some horses as a result of upper respiratory muscle paralysis. Once episodes subside, horses regain their feet and appear normal with absent or minimal gait abnormalities. Young horses that are homozygous for the HyPP trait may have respiratory stridor and periodic obstruction of the upper respiratory tract.

Common factors that trigger episodes include sudden dietary changes or ingestion of diets high in potassium (>1.1%), such as those containing alfalfa hay, molasses, electrolyte supplements, and kelp-based supplements. Fasting, anesthesia or heavy sedation, trailer rides, and stress may also precipitate clinical signs. The onset of signs, however, is often unpredictable. Exercise per se does not appear to stimulate clinical signs; serum CK shows no or minimal increases during episodic fasciculations and weakness.

Descent from the stallion Impressive in a horse with episodic muscle tremors is strongly suggestive of HyPP. Hyperkalemia (6-9 mEq/L), hemoconcentration, and hyponatremia are seen during clinical episodes, but a definitive diagnosis requires DNA testing of mane or tail hair. Electromyographic examination of affected horses between attacks reveals abnormal fibrillation potentials and complex repetitive discharges, with occasional myotonic potentials and trains of doublets between episodes. Differential diagnoses for hyperkalemia include delay before serum centrifugation, hemolysis, chronic renal failure, and severe rhabdomyolysis.

Many horses recover spontaneously from HyPP episodes. Owners may abort early mild episodes using low-grade exercise or feeding grain or corn syrup to stimulate insulin-mediated movement of potassium across cell membranes. In severe cases, administration of calcium gluconate (0.2-0.4 mL/kg of a 23% solution diluted in 1 L of 5% dextrose) or IV dextrose (6 mL/kg of a 5% solution), alone or combined with sodium bicarbonate (1-2 mEq/kg), often provides immediate improvement. With severe respiratory obstruction, a tracheostomy may be necessary. Acute death is common, especially in homozygous animals.

Prevention requires decreasing dietary potassium to 0.6-1.1% total potassium concentration and increasing renal losses of potassium. High-potassium feeds such as alfalfa hay, brome hay, canola oil, soybean meal or oil, sugar molasses, and beet molasses should be avoided. Optimally, later cuts of timothy or bermuda grass hay; grains such as oats, corn, wheat, and barley; and beet pulp should be fed in small meals several times a day. Regular exercise and/or frequent access to a large paddock or yard are also beneficial. Pasture is ideal for horses with HyPP because the high water content of pasture grass makes it unlikely that horses will consume large amounts of potassium in a short period of time. Complete feeds for horses with HyPP are commercially available. For horses with recurrent episodes even with dietary alterations, acetazolamide (2-4 mg/kg, PO, bid-tid) or hydrochlorothiazide (0.5-1 mg/kg, PO, bid) may be helpful. Breed registries and other associations have restrictions on the use of these drugs during competitions.