Heritable Muscle Diseases

CHAPTER 103 Heritable Muscle Diseases


Hyperkalemic periodic paralysis (HyPP) is an autosomal dominant trait affecting Quarter Horses, American Paint Horses, Appaloosas, and crossbred Quarter Horses. It was the first equine disease attributed to a specific genetic mutation. A single base-pair substitution in the SCN4A gene causes a phenylalanine/leucine substitution in a key part of the voltage-dependent skeletal muscle sodium-channel α-subunit. A prolific Quarter Horse sire born in 1969, named Impressive, appears to have been the origin of the HyPP mutation. Impressive and his 355,000 registered descendants are usually heavily muscled and have therefore dominated the halter horse industry. Approximately 4% of the Quarter Horse breed may carry the mutation, but most are heterozygous; however, some horses are homozygous for this dominant trait. It is highly advisable to perform genetic testing on horses related to Impressive during a prepurchase examination or before heavy sedation and anesthesia. Owners should be fully aware that breeding an affected horse to a normal horse results in a 50% chance of perpetuating the disorder in future generations.


Horses with HyPP should be fed a balanced diet containing between 0.6% and 1.1% total potassium concentration by weight. Each meal should contain less than 33 g of potassium. High-potassium feeds such as alfalfa hay, orchard grass hay, brome hay, soybean meal, 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. The potassium concentration of forages can vary widely, so it may be prudent to perform a forage analysis to determine potassium concentrations. Regular exercise or frequent access to a large paddock or yard is also beneficial. Although potassium concentrations may be high in grasses, the high water content in this forage appears to dilute the potassium load, making them safe for pastured horses. Commercially available complete feed with a guaranteed K+ content may be more convenient for some HyPP horses.

Acetazolamide (2 to 3 mg/kg orally [PO], every 8 to 12 hours) or hydrochlorothiazide (0.5 to 1 mg/kg PO, every 12 hours) may be indicated for horses in which episodes are not controlled by adjusting the diet. These diuretics increase renal potassium excretion, and acetazolamide also stimulates insulin secretion, which drives blood glucose and potassium into cells. Breed registries and other associations may have restrictions on the use of these drugs during competitions because diuretics may mask prohibited substances. In most cases HyPP is a manageable disorder.


Glycogen branching enzyme deficiency (GBED) is an autosomal recessive glycogen storage disorder that affects neonatal Quarter Horse or Paint Horse foals or aborted fetuses. The disease is due to a mutation in the GBE1 gene, which markedly reduces the function of the glycogen branching enzyme. As a result, tissues such as cardiac and skeletal muscle, the liver, and the brain cannot store and mobilize glycogen to maintain normal glucose homeostasis. Carriers of GBED trace back to the sire King P234 in most cases; however, King’s sire Zantanon may also have carried GBED. Most Quarter Horses, however, are descendants of these two stallions, so pedigree analysis is not very helpful. GBED has likely been carried in the Quarter Horse breed at least since its inception in 1940. Approximately 8% of both Quarter and Paint Horses are carriers of GBED. Homozygous GBED fetuses were detected in 2% to 4% of second- and third-trimester abortions submitted to two diagnostic laboratories. Many horses with GBED likely remain undiagnosed because of the similarity of clinical signs between GBED and many neonatal diseases and the current lack of genetic testing or because fetuses are stillborn or aborted.


Polysaccharide storage myopathy (PSSM) was first identified in Quarter Horse–related breeds in 1992 and is characterized by twofold higher glycogen concentrations and abnormal granular amylase-resistant inclusions in skeletal muscle. Several different acronyms have been used to describe PSSM, including EPSM and EPSSM. The variety of acronyms used are in part related to preferences of different laboratories as well as to differences in the criteria used to diagnose PSSM. The prevalence of PSSM in Quarter Horses is approximately 12% and in Belgians and Percherons is approximately 35%. recently, an autosomal dominant point mutation in the glycogen synthase 1 gene (GYS1) has been identified that appears to cause unregulated synthesis of glycogen. This GYS1 mutation, present in horses for over a 1000 years, is the same disorder described as “Monday morning disease” or “azoturia” in draft horses in the early twentieth century.

The GYS1 mutation is found in Quarter Horses and five draft horse breeds, Paint horses, Appaloosa horses, three Warmblood breeds, Haflinger, Morgan, Mustang, Rocky Mountain Horse, and Tennessee Walking Horse breeds, as well as mixed breed horses. When all horses diagnosed with PSSM at the University of Minnesota Neuromuscular Diagnostic Laboratory by muscle biopsy were screened for the genetic mutation, it was clear that there was a subset of horses with PSSM that did not have the GYS1 mutation. Nomenclature for PSSM therefore has changed; type 1 PSSM refers to horses with the GYS1 mutation, and type 2 PSSM refers to horses diagnosed with abnormal glycogen storage in muscle biopsy that lack the GYS1 mutation. Type 2 PSSM occurs in about 28% of Quarter Horses and in a wide variety of Warmblood breeds, such as Dutch Warmbloods, Hannoverian, Westfalian, Canadian Warmblood, Irish Sport Horse, Gerdlander, Hussien, and Rheinlander. The true prevalence in Warmbloods is unknown. A small percentage of light-breed horses may also be afflicted with type 2 PSSM.

Clinical Signs

May 28, 2016 | Posted by in EQUINE MEDICINE | Comments Off on Heritable Muscle Diseases
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