Fatal Genetic Disorder in Quarter Horse Foals Identified

Research has identified a genetic mutation that leads to glycogen branching enzyme deficiency, a fatal condition in Quarter Horse foals. By Laurie Bonner for EQUUS magazine.
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Breakthrough research at the University of Minnesota has identified the genetic mutation that leads to a fatal condition in Quarter Horse foals, making it possible to determine whether individual horses can pass the condition on to their offspring. Foals with the disorder, called glycogen branching enzyme deficiency (GBED), are unable to fully utilize glucose, the body's primary source of energy.

To store energy in the muscles, the body converts glucose, which consists of sugar molecules assembled in long, straight chains, into glycogen, glucose chains arranged in a treelike, branched structure. When the body needs energy, it breaks a sugar molecule off the end of one of the branches.
GBED, however, prevents the production of the enzyme that converts glucose into glycogen, so cells contain only straight chains of sugar molecules.

"If there are no branches, there would be few endpoints to pick off for energy," explains Stephanie Valberg, DVM, PhD, of the University of Minnesota. "When the cell has no energy to run its many functions, it dies. The muscles run out of energy quickly and they become weak, or the brain has no sugar and goes into seizure, or the heart runs out of sugar and stops beating." GBED is always fatal; affected foals may be stillborn or die up to two months after birth.

In a series of studies funded in part by the American Quarter Horse Association, Valberg and her team first identified GBED in foals in 2001. Two years later, they located the gene responsible for the production of glycogen branching enzyme on equine chromosome 26.

Next, the researchers identified the mutation in the gene that causes GBED and sought to determine how GBED is inherited by looking for the mutated gene in foals with the disorder as well as in their close relatives. They evaluated the DNA of 11 foals with GBED as well as that of eight of their dams, six of their sires, three half-siblings, one full sibling and 16 healthy, unrelated control Quarter Horses.

They found that GBED is a recessive trait. All of the foals who died as a result of GBED were found to be homozygous for the mutated gene, meaning that they had received a copy from each parent. All of the parents tested proved to be heterozygous carriers of the mutation, meaning that they carried one normal and one mutated copy of the gene.

All of the siblings carried either one copy of the mutated gene or none; none of the control horses carried a mutation. Heterozygous carriers are unaffected by the disease, but when two carriers are mated, they have a 25 percent chance of producing a foal with GBED. Although to date only a small number of foal deaths have been attributed to GBED, Valberg believes that the disease may be more common than people realize.

"It can be confused with infections like sepsis or neonatal maladjustment," Valberg says. "Some farms lose foals from weakness, sepsis and contracted tendons due to hypothyroidism, but farms with hypothyroidism often have many foals affected in a breeding season, while cases of GBED are more sporadic. Many times foals die suddenly and no cause is found at postmortem."

Outward signs of GBED, which vary depending on the organs most affected, include low birth weight, a high respiratory rate, seizures, contracted tendons, generalized weakness, recumbency and sudden death.

All of the foals with GBED identified in the Minnesota studies were Quarter Horses, but they were not necessarily closely related--in some cases shared ancestors did not appear until the ninth generation. The prevalence of GBED remains to be determined, but Valberg estimates that between 5 and 10 percent of Quarter Horses and related breeds may carry it.

"There are many relatives out there to the few foals we have identified--more than 2,000 half brothers and sisters," she says, adding that current research is focused on determining how common the GBED mutation is in Quarter Horses.

However, now that the mutation that causes GBED has been identified, says Valberg, "we can easily and accurately test for the disease from hair or blood samples." It is also possible to detect carriers of a single copy of the gene.

"If you feel that this is a potential problem in your horses, the only way to know is to do a DNA test," Valberg says. "There is no way to diagnose the condition from pedigrees alone."

Visit the University of Minnesota College of Veterinary Medicine website for DNA-based testing information.

This article originally appeared in the September 2004 issue of EQUUS magazine.

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