GM1 gangliosidosis (GLB1 gene, Shiba)

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 between 5 and 6 months of age, and may include weight loss, muscle weakness and blindness. When ganglioside accumulation is severe, the dog`s coordination is impaired and cerebellar ataxia and limb weakness often occur. 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

GM1 gangliosidosis is a disease that affects the brain and other tissues and is caused by alterations in the enzyme acid beta galactosidase which is encoded by the GLB1 gene. This enzyme plays a vital role in the breakdown and recycling of complex molecules within cell lysosomes. When there is deficiency in beta galactosidase activity, accumulation of glioconjugates in lysosomes occurs, especially in cells of the central nervous system triggering GM1. A mutation in the GLB1 gene responsible for GM1 has been identified in the Shiba breed and is homologous to a human form of late-infantile/juvenile gangliosidosis. The variant discovered is a deletion of a cytosine (c.1649delC) in exon 15 that causes premature termination of protein translation and results in an abnormal amino acid sequence. In addition to this variant, two others have also been identified in the Alaskan Husky and Portuguese Water Dog breeds.

Most affected breeds

Shiba
Beagle
Alaskan Husky
Portuguese Water Dog
English Springer Spaniel

Bibliography

Pervin S, Islam MS, Yorisada Y, et al. Carrier Rate and Mutant Allele Frequency of GM1 Gangliosidosis in Miniature Shiba Inus (Mame Shiba): Population Screening of Breeding Dogs in Japan. Animals (Basel). 2022 May 12;12(10):1242.

Yamato O, Endoh D, Kobayashi A, et al. A novel mutation in the gene for canine acid beta-galactosidase that causes GM1-gangliosidosis in Shiba dogs. J Inherit Metab Dis. 2002 Oct;25(6):525-6.