Glycogen branching enzyme deficiency in quarter horse foals.

The research article discusses the occurrence and investigation of Glycogen Branching Enzyme (GBE) deficiency in seven Quarter Horse foals, highlighting the varying clinical signs, the biochemical analysis of tissues, and genetic implications of this disorder. The study suggests that GBE deficiency could be a significant cause of neonatal horse mortality, often misdiagnosed due to the diverse clinical symptoms.

Research Background and Purpose

• The research was conducted after observing the unusual high death rate among Quarter Horse foals by the age of seven weeks. The researchers noticed clinical signs ranging from stillbirth, seizures, and respiratory or cardiovascular failure to continual lying down (recumbency).
• The purpose of the study was to examine the potential cause of these signs, specifically looking at the possible deficiency of a crucial enzyme known as the Glycogen Branching Enzyme (GBE).

Methods and Findings

• Several clinical tests were carried out on the foals, revealing leukopenia (low white blood cell count), along with high levels of serum creatine kinase (CK), aspartate transaminase (AST), and gamma glutamyl transferase (GGT) in most foals. Two foals also had intermittent episodes of hypoglycemia (low blood sugar).
• Postmortem examinations noted minimal gross lesions but lung edema in two foals. Muscle, heart or liver samples exhibited abnormal globular or crystalline inclusions.
• A biochemistry-related test presented an accumulation of an unbranched polysaccharide, a complex carbohydrate, in the tissues of the foals. Further analysis stated that total polysaccharide concentrations in skeletal muscle were 30% less, but normal in the liver and heart.
• While levels of several glycolytic enzymes were normal, the activity of the GBE enzyme was virtually non-existent in various tissues, indicating GBE deficiency.

Genetic Connections and Implications

• The study found that GBE enzyme levels in the blood cells of the foals’ mothers and several of their half or full siblings were around 50% of the control level.
• By using Western blot, a technique to detect specific proteins, it was found that GBE proteins in the liver of the affected foals were significantly reduced or absent.
• Pedigree analysis of the horses supported that the lack of GBE occurs due to an autosomal recessive mode of inheritance, meaning that a horse can be a carrier for the deficiency without showing symptoms.
• The researchers raised concerns regarding the overall horse population, given that the affected foals have more than 2,600 half-siblings. They emphasized that GBE deficiency may be a significant, yet overlooked, cause of death in neonatal Quarter Horses due to the varied clinical symptoms.