Glycogen Branching Enzyme Deficiency
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Glycogen-branching enzyme deficiency (GBED) is an inheritable
glycogen storage disease A glycogen storage disease (GSD, also glycogenosis and dextrinosis) is a metabolic disorder caused by an enzyme deficiency affecting glycogen synthesis, glycogen breakdown, or glucose breakdown, typically in muscles and/or liver cells. GSD has ...
affecting
American Quarter Horse The American Quarter Horse, or Quarter Horse, is an American breed of horse that excels at sprinting short distances. Its name is derived from its ability to outrun other horse breeds in races of a quarter mile or less; some have been clocked at s ...
s and
American Paint Horse The American Paint Horse is a breed of horse that combines both the conformational characteristics of a western stock horse with a pinto spotting pattern of white and dark coat colors. Developed from a base of spotted horses with Quarter Horse ...
s. It leads to abortion, stillbirths, or early death of affected animals. The human form of the disease is known as
glycogen storage disease type IV Glycogen storage disease type IV (GSD IV), or Andersen's Disease, is a form of glycogen storage disease, which is caused by an inborn error of metabolism. It is the result of a mutation in the GBE1 gene, which causes a defect in the glycogen branc ...
.


Pathophysiology

Glycogen Glycogen is a multibranched polysaccharide of glucose that serves as a form of energy storage in animals, fungi, and bacteria. The polysaccharide structure represents the main storage form of glucose in the body. Glycogen functions as one o ...
is a molecular
polymer A polymer (; Greek '' poly-'', "many" + ''-mer'', "part") is a substance or material consisting of very large molecules called macromolecules, composed of many repeating subunits. Due to their broad spectrum of properties, both synthetic a ...
of
glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, using ...
used to store energy. It is important for providing energy for skeletal and cardiac muscle contraction, and for maintaining glucose
hemostasis In biology, hemostasis or haemostasis is a process to prevent and stop bleeding, meaning to keep blood within a damaged blood vessel (the opposite of hemostasis is hemorrhage). It is the first stage of wound healing. This involves coagulation, whi ...
in the blood. Molecules of glucose are linked into linear chains by α-1,4-
glycosidic bonds A glycosidic bond or glycosidic linkage is a type of covalent bond that joins a carbohydrate (sugar) molecule to another group, which may or may not be another carbohydrate. A glycosidic bond is formed between the hemiacetal or hemiketal grou ...
. Additionally, branches of glucose are formed off of the chain via α-1,6-glycosidic bonds. 2 molecules of glucose are joined into an α-1,4-glycosidic bonds by an enzyme known as
glycogen synthase Glycogen synthase (UDP-glucose-glycogen glucosyltransferase) is a key enzyme in glycogenesis, the conversion of glucose into glycogen. It is a glycosyltransferase () that catalyses the reaction of UDP-glucose and (1,4--D-glucosyl)n to yield UD ...
. This bond may be broken by
amylase An amylase () is an enzyme that catalyses the hydrolysis of starch (Latin ') into sugars. Amylase is present in the saliva of humans and some other mammals, where it begins the chemical process of digestion. Foods that contain large amounts of ...
when the body wishes to break down glycogen into glucose for energy.
Glycogen branching enzyme 1,4-alpha-glucan-branching enzyme, also known as brancher enzyme or glycogen-branching enzyme is an enzyme that in humans is encoded by the ''GBE1'' gene. Glycogen branching enzyme is an enzyme that adds branches to the growing glycogen molecul ...
is responsible for the required α-1,6-glycosidic bonds needed to start a branch off of these linear chains. These branches are important, as they provide additional "free ends" for linear chains of α-1,4-glycosidic bonds, which can then be broken down by amylase. This allows for glucose to be removed at a faster rate than if all glucose molecules were in a single chain with only two free ends on which amylase could attach. GBED is caused by an
autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...
mutation to the GBE1 gene, which leads glycogen branching enzyme activity that is reduced to absent. Subsequently, glycogen molecules are produced with few branches, which greatly decreasing the number of nonreducing ends, drastically slowing the rate at which the molecule can be synthesized or broken down. This causes low levels of muscle glycogen that is very resistant to amylase.


Clinical signs

Lacking proper glycogen storage, the horse's brain, heart muscle, and skeletal muscles cannot function, leading to rapid death. Most foals with GBED are aborted (usually in the second trimester), or are stillborn, and those that survive live only for a few months. Symptoms include general weakness, contracted tendons,
hypoglycemic Hypoglycemia, also called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose belo ...
seizures, cardiac arrest, and sudden death. Horses that are heterozygous for the GBED allele have been shown to have glycogen branching enzyme activity levels that were half that of an unaffected horse. However, there is no abnormal
phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological proper ...
in these heterozygous carriers.


Diagnosis, treatment, and prevention

This condition may be diagnosed with a muscle biopsy from affected animals. There is no treatment. Because the disease is autosomal recessive, affected foals must be
homozygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mo ...
for the lethal GBED allele, meaning both parents must be
heterozygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mo ...
for the allele. A
blood test A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a hypodermic needle, or via fingerprick. Multiple tests for specific blood components, such as a glucose test or a cholester ...
for this allele was developed by the
University of Minnesota The University of Minnesota, formally the University of Minnesota, Twin Cities, (UMN Twin Cities, the U of M, or Minnesota) is a public university, public Land-grant university, land-grant research university in the Minneapolis–Saint Paul, Tw ...
College of Veterinary Medicine and is licensed to the
UC Davis The University of California, Davis (UC Davis, UCD, or Davis) is a public land-grant research university near Davis, California. Named a Public Ivy, it is the northernmost of the ten campuses of the University of California system. The institut ...
Veterinary Genetics Laboratory. Using this, breeders can avoid crosses that could produce GBED foals, and eventually selectively breed it out. Carrier frequency has been estimated at 7.1% in the Quarter Horse, 8.3% in the Paint Horse, and as high as 26% in Western Pleasure horses. This genetic disease has been linked to the foundation Quarter Horse sire
King P-234 King (1932–1958), often known as King P-234, was an outstanding early Quarter Horse stallion who influenced the breed throughout the early years of the American Quarter Horse Association (or AQHA). Life King was born June 25, 1932, the offsp ...
.


References

"Testing for Genetic Diseases" ''Equus 353'', pp 40–41.


External links

{{Commonscat
University of Minnesota: Neuromuscular Diagonistic Laboratory: Glycogen Branching Enzyme Deficiency (GBED)
* ttp://www.vetgen.com/equine-gbed-service.html VetGen: Veterinary Genetics Services: Glycogen Branching Enzyme Deficiency (GBED) Horse diseases American Quarter Horses