GM2 Gangliosidosis (HEXB gene, Toy Poodle)

Gangliosidoses in dogs are a group of rare lysosomal storage diseases that result in the abnormal accumulation of a fatty substance called ganglioside in the brain and other body organs such as the liver. There are two main forms of gangliosidosis in dogs: the GM1 form and the GM2 form, caused by deficiency in the enzymes acid galactosidase and β-hexosaminidase, respectively.

Symptoms

Symptoms of gangliosidosis usually appear during the first two years of life and may include weight loss, muscle weakness and blindness. When ganglioside accumulation is severe, the dog's coordination is affected and cerebellar ataxia often occurs. The dog may appear lethargic or depressed. Head jerking is often observed, especially when eating. Seizures may occur in some cases. Symptoms worsen with time and euthanasia is often resorted to.

Disease Management

Currently, there is no cure for gangliosidosis in dogs. Treatment focuses on alleviating symptoms and improving the animal's quality of life. If you suspect that your dog may be affected by this disease, it is important that you take your dog to a veterinarian specializing in veterinary neurology for proper diagnosis and treatment.

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

The GM2 gangliosidoses are a group of lysosomal storage diseases characterized by the accumulation of GM2 ganglioside and related glycolipids, mainly in neurons. GM2 ganglioside requires removal of the terminal N-acetyl-galactosamine (GalNAc) residue by β-hexosaminidase to be metabolized. The β-hexosaminidase is composed of an α-subunit and a β-subunit encoded by HEXA and HEXB, respectively. Certain mutations in HEXA and HEXB are responsible for GM2 gangliosidoses. The variant analyzed here, c.391del of the HEXB gene, was described in Toy Poodle or Toy Poodle breed dogs. The c.391del variant results in the deletion of a guanine (G) leading to a premature stop codon and a truncated protein.

Most affected breeds

Golden Retriever
Mixed breed
Shiba Inu
Toy Poodle

Bibliography

Rahman MM, Chang HS, Mizukami K,et al. A frameshift mutation in the canine HEXB gene in toy poodles with GM2 gangliosidosis variant 0 (Sandhoff disease). Vet J. 2012 Dec;194(3):412-6.