English
Glycogen branching enzyme deficiency (GBED) is a fatal disorder caused by a gene mutation found in the Quarter Horse and Paint Horse bloodlines.
GBED causes abortion in late-term pregnancies, stillbirth or severe muscle weakness and eventually death in newborn foals.
GBED prevents foals from properly storing sugars in the body. As a result, there is not enough energy to fuel the important organs and muscles of the body. This causes severe weakness and other clinical signs.
Genetic testing for diseases is required for most QH and APH horses in breeding programs to ensure healthy offspring and prevent financial loss associated with losing a foal.
Glycogen Branching Enzyme Disease in Horses
GBED is a fatal and incurable condition caused by the lack of glycogen branching enzyme (GBE) in the horse’s body.
GBE is involved in making glycogen, a storage form of glucose. Without GBE, normal glycogen can not be formed. Instead, abnormal glycogen forms which can not be broken down to provide energy. This impairs the function of the horse’s skeletal muscles, heart, and brain.
Fetuses with GBED are usually stillborn or aborted in late-term pregnancy. Foals that survive birth typically die or are humanely euthanized by eight weeks of age. [1]
Prevalence
GBED is an autosomal recessive trait that affects the foal when both parents carry a copy of the mutated GBE1 gene. [2] Horses can be carriers of the disorder without presenting symptoms.
Approximately 8% of Quarter Horses (QH) and 7% of American Paint Horses (APH) are believed to carry the GBED mutation. [3][2] The allele for GBED is also commonly found in western pleasure, working cow horses and cutting horses.
Recent studies indicate that GBED is becoming more prevalent in affected breeds. Diligent efforts to control the breeding of carrier horses must be implemented. [4]
Clinical Signs
Clinical signs of GBED can be difficult to recognize as they mimic other diseases that commonly affect foals.
Foals that survive to term can demonstrate the following signs of GBED: [6][7][8]
- Weakness & lethargy
- Inability to stand or nurse
- Low body temperature or hypothermia
- High serum CK, AST and GGT
- Extended periods of recumbency
- Contracted tendons in all legs
- Seizures
- Fast breathing & respiratory failure
- Cardiac failure
- Sudden collapse or death
Foals can seem healthy for short periods of time before becoming very sick. Affected foals often need warming after birth. [6]
If foals are too weak to nurse or bottle-feed regularly, hypoglycemic seizures or heart failure can occur.
Unlike other genetic muscle disorders, foals with GBED do not develop firm and painful muscles. [8]
If you suspect your foal has GBED or another genetic condition, contact your veterinarian immediately for examination and diagnosis.
What Causes GBED in Horses?
Normal Glycogen Synthesis
Glycogen is a form of glucose stored in the liver and muscles to provide energy to those tissues and the rest of the body.
Glycogen is broken down to release glucose molecules for skeletal and cardiac muscle contraction, and to maintain stable blood glucose levels. [9]
The Glycogen Branching Enzyme (GBE) adds branches to the glycogen structure. This enzyme generates α-1,6-glucosidic branches from α-1,4-linked glucose chains.
In a normal horse, the GBE1 gene encodes a functional glycogen branching enzyme to synthesize glycogen. This allows the horse’s cells to store sugars needed for energy.
The GBED mutation
Horses with GBED have a nonsense mutation in codon 34 of the GBE1 gene. This stops protein synthesis and results in no functional GBE found in the cells. This leads to the production of abnormal glycogen molecules, which lacks the branching structure. [10]
This mutation inhibits glycogenolysis, which is the breakdown of glycogen into glucose. Abnormal glycogen molecules accumulate in the liver and muscles, resembling large granules with fewer branch points. [9]
As a result, glycogen cannot be used effectively. [1][11] Blood sugar regulation is dysfunctional, and the horse does not have adequate energy to fuel muscle contractions and other processes.
Newborn foals are particularly sensitive to changes in glycogen homeostasis. Organ dysfunction and extreme muscle weakness can occur shortly after birth. [6][11]
Other Breeds
There are no known or verified cases of GBED outside of the QH and APH breeds. [6] Researchers suggest that breeds descending from the QH, such as the Appaloosa, may be affected. However, there is a lack of evidence for this claim.
While it has been suggested that Thoroughbreds may be affected by GBED, there is no evidence of this genetic disorder in the breed. The original American Quarter Horse Association (AQHA) included Thoroughbreds in their breed registry, as long as their coat colours met their requirements. [1]
The original ancestor of the mutated gene likely belonged to the Quarter Horse or paint pedigree, likely in the early 1900s. Fortunately, this stallion has not been found in any Thoroughbred pedigrees. [1]
Diagnosis
QH or APH foals that present clinical signs of GBED from birth should be suspected of having GBED. [8] Since the disorder is not sex-linked, both colts and fillies are affected equally. [6]
Consult your veterinarian to confirm a suspected diagnosis and rule out other conditions. A skeletal muscle biopsy and other lab tests may be required.
Genetic Testing
When a carrier dam is bred to a carrier stallion, there is a 25% chance of the foal having GBED. Therefore, genetic testing of the parents is recommended if QH or APH are used in a breeding program.
Lab technicians will analyze mane or tail hair samples to identify whether horses are carriers of GBED.
The average cost for GBED testing is $100 but can vary between laboratories. [6] You will be asked to submit a few strands of hair (10 or more) with roots intact for genetic testing.
Muscle Biopsy & Staining
Initial diagnosis of GBED is usually made using periodic acid-Schiff (PAS) staining of skeletal (or cardiac) muscle. [8]
In comparison to the muscle tissue of a normal horse, muscle samples from foals with GBED have a characteristic staining pattern. [6] The background of normal tissue stains pink, whereas GBED-affected muscle contains large clumps of purple without a pink background.
The hindlimb muscles of foals with GBED often have extensive muscle fiber degeneration or necrosis prior to euthanasia. Conducting a biopsy on affected muscles can help confirm diagnosis. [9]
Carriers of the GBE1 mutation have limited (50%) GBE activity compared to healthy control horses. However, they do not show clinical signs of the disease. [9]
GBE activity is noticeably reduced in blood, muscle and liver tissue samples from affected foals. [10] These foals cannot form or store normally branched glycogen, which prevents glycogenolysis and the release of glucose. [3]
Post-mortem liver or muscle analysis can also be done to determine whether a foal was affected by GBED.
Blood Work
Blood samples can be used to assist in diagnosing foals with GBED. Affected foals may have low white blood cell count, low blood glucose and moderate-high serum creatine kinase (CK), aspartate transaminase (AST) and gama glutamyl transferase (GGT) levels. [2]
When glucose levels drop below normal, bodily functions that require sugars begin to shut down. Intermittent hypoglycemia can be identified when measuring blood glucose levels in GBED foals. [9]
Other Findings
Several findings from individual case reports in foals with GBED have assisted with diagnosis.
Following sudden recumbency at eight weeks, one filly was found to have monocytosis – abnormally elevated levels of infection-fighting monocytes indicating inflammation in the body. [9]
Elevated triglycerides alongside increased liver and muscle enzymes can also indicate damage to muscle cells and increased requirements for fatty acids. This can occur when glucose is not available for energy.
Researchers have proposed that some foals with GBED may exhibit nervous system dysfunction due to a lack of glucose supply to the brain. [9] However, this does not occur in all foals.
It is unknown whether gait incoordination and awkward movement in affected foals are caused by muscle weakness or brain dysfunction. [9]
Management
There is no treatment or cure for horses born with GBED. Euthanasia is warranted in many cases, and most affected foals die or are euthanized by eight weeks of age. [1]
One foal survived until 18 weeks with extensive care from handlers. [9]<