Glycogen Storage Disease Type IIIa (AGL gene)

Glycogen storage disease (GSD) is a group of inherited metabolic disorders in which there is an abnormal accumulation of glycogen in body tissues. These diseases are caused by defects in enzymes necessary for the synthesis or breakdown of glycogen.

Symptoms

GSD type III is clinically and enzymatically varied, with symptoms including hepatomegaly, hypoglycemia, fasting ketosis, skeletal myopathy and cardiomyopathy. Dogs affected by GSD IIIa show an increase in ALT, ALP and CK during their first year of life. At 14 months, they may begin to show fatigue, exercise intolerance and fainting after physical activity.

Disease Management

The treatment and prognosis of glycogen storage disease (GSD) in dogs varies depending on the type and severity of the condition. Genetic testing can be helpful in confirming the disease and determining the specific type of GSD.

Genetic basis

This disease follows an autosomal recessive mode of inheritance. Autosomal recessive inheritance means that the dog, regardless of sex, must receive two copies of the mutation or pathogenic variant to be at risk of developing the disease. Both parents of an affected dog must carry at least one copy of the mutation. Animals with only one copy of the mutation are not at increased risk of developing the disease, but may pass the mutation on to future generations. Breeding between dogs carrying genetic variants that can cause disease, even if they do not show symptoms, is not recommended.

Technical report

Glucose is stored in tissues in the form of glycogen, a large homopolymer of glucose residues that is catabolized by the release of glucagon through the activities of phosphorylase and glycogen debranching enzyme. Deficiency of glycogen debranching enzyme activity results in abnormal glycogen particles. Gregory et al. identified that the c.4223del mutation in the AGL gene that codes for this debranching enzyme causes AGL IIIa in curly-haired retriever dogs when present in homozygosis. This mutation is a deletion of an adenosine (A) in exon 32 of AGL that results in a reading frame shift and a truncated protein.

Most affected breeds

Curly-coated retriever

Bibliography

Gregory BL, Shelton GD, Bali DS, Chen YT, Fyfe JC. Glycogen storage disease type IIIa in curly-coated retrievers. J Vet Intern Med. 2007 Jan-Feb;21(1):40-6.