Page 72 - October 2016

GBED
Glycogen Branching Enzyme Deficiency: A Genetic Muscle Disease that Kills Foals
Foals with this disorder are unable to fully utilize glucose—the body’s primary source of energy.
by Heather Smith Thomas
Agenetic mutation that occurred at least 60 years ago and affecting an unknown number of horses descending from the original indi- vidual was finally identified in 2004. The inherited defect first came to light in the spring of 1997, when muscle biopsies from a foal at Kansas State University were submitted to the Neuromuscular Diagnostic Laboratory at University of Minnesota. It took a few more years, however, to pinpoint the problem. This foal and others with similar symptoms were found to have the same fatal condition.
At the Minnesota lab, Dr. Stephanie Valberg (Professor and Director of University of Minnesota’s Equine Center at that time) in 2001 found that these foals’ muscles had a lower than normal amount of glycogen and an overabundance of abnormal polysaccharide within the cells. After this discovery, researchers realized that some of the late term abor- tions of unknown cause, stillbirths, and weak foals that died soon after birth had probably been due to this condition.
More recent research suggests that at least 3% of abortions in Quarter Horses are caused by GBED, and that this defect may now be present in about 10% of all Quarter Horses and related bloodlines, such as Paints and Appaloosas that have incorpo- rated certain Quarter Horse bloodlines. Some of the affected foals are alive at birth, but are very weak and may require help to stand and nurse. If blood tests are taken, GBED foals often have a low white blood cell count. These foals may have low blood glucose and high muscle enzymes CK and AST and the liver enzyme GGT.
They may seem healthy for the first hours or days, but then die suddenly, or develop seizures or become weak and are unable to get up. None of these foals have survived. With aggressive treatment and assistance, some have lived for a few months, but all known cases have died or have been euthanized by about two or three months of age.
Dr. Valberg and Dr. James Mickelson (Professor of Veterinary Pathobiology) at the UM laboratory found that these foals were all related, sharing a com- mon ancestor, and all of them had an abnormal sugar within their skeletal muscles. They all had a genetic defect called glycogen branching enzyme deficiency (GBED). This enzyme is responsible for forming the glycogen that provides energy for body tissues. Foals with this disorder are unable to fully utilize glucose— the body’s primary source of energy.
In order to store energy in the muscles, the body converts glucose (long straight chains of sugar mol- ecules) to glycogen, which consists of glucose chains arranged in a 12-tiered branching tree-like structure with thousands of branch points. Whenever the body (such as a muscle) needs energy, a sugar molecule is removed from one of these branches. This allows for rapid mobilization of glucose for energy metabolism.
But in a foal with GBED, the special enzyme
that converts glucose into glycogen and arranges the branch points is not produced. Thus, the muscle cells contain only the straight chains of sugar molecules and there are no end points to pick off, for energy. The lack of branch points on the glycogen molecule, due to the missing enzyme, means that the foal’s body tissues cannot efficiently store and metabolize glucose. As explained by Dr. Valberg, when a cell has no energy for its many functions, it dies. Thus, the muscles are losing cells, running out of energy, and become weak. The tissues that rely heavily on glyco- gen as a fuel include skeletal muscle, heart muscle, and the brain. If the brain runs out of sugar, or the foal has low blood sugar, this may result in seizures. If the heart runs out of sugar it stops beating. Therefore, GBED is always fatal.
Horses are not the only species in which GBED has been found. Humans and Norwegian forest cats also have this mutation present in their respective gene pools. In humans, this disease is called GSD IV (glycogen storage disease type IV).
70 SPEEDHORSE, October 2016
equine health