What is Gangliosidosis in dogs?

Gangliosidosis (GM1), also known as ganglioside storage disease, is an inherited disease in dogs that results in the storage of gangliosides thoughout the nervous system of the dog. Affected dogs lack the enzyme galactosidase that is required by the dog to break down complex carbohydrates, leading to the accumulation of ganglioside in the cells. Ganglioside accumulates in the cells of the brain, spinal cord and autonomic ganglia of the nervous system and it is this accumulation that prevents the normal function of the nervous system. The brain is the most severely affected of the organs. Gangliosidosis (GM1) has no cure and will ultimately lead to the death of the affected dog.

Genetics of Gangliosidosis (GM1) in dogs

Gangliosidosis (GM1) results from point mutations in the GLB1 gene in dogs and has an autosomal recessive pattern of inheritance. Affected dogs have 2 copies of the mutated GLB1 gene in their genome. Dogs that have only one faulty copy of the gene responsible are called carriers as they can pass on the disease to their offspring if they are bred to another carrier or affected dog. Dog with no mutated copies of the gene responsible for Gangliosidosis (GM1) are called ‘clear’ and cannot have offspring that are affected by Gangliosidosis (GM1) regardless of how many (if any) copies the dog they are bred with have.

What is the severity of Gangliosidosis (GM1)?

Gangliosidosis (GM1) is a very severe disease in dogs as it will greatly reduce the quality of life and the length of an affected dog’s life also. Most affected dogs will only live for less than a year at best with many owners choosing to euthanase their affected dog before this stage.

What are the symptoms of Gangliosidosis (GM1) in dogs?

The symptoms of Gangliosidosis (GM1) begin to show themselves early in the life of an affected puppy. 4 to 5 months old is generally when the signs are apparent that something is wrong with the dog. The symptoms are progressive and unrelenting. Light symptoms will become more pronounced as the disease progresses. Typical symptoms include lethargy, vision problems, paralysis of the extremities, spasticity of the muscles, head tremors, difficulty walking, abnormal bone growth and weight loss. These symptoms progress very quickly to their fatal conclusion in a matter of months.

Diagnosis of Gangliosidosis in dogs

Diagnosis of Gangliosidosis in dogs is only definitively made with the use of a DNA Disease Screen to identify the mutated GLB1 gene in affected dogs. Blood tests and other work may help to indicate Gangliosidosis but a DNA test is the only truly definitive method of diagnosis.

Treatment of dogs with Gangliosidosis

Currently there is no viable treatment for dogs affected by Gangliosidosis and a cure seems a long way off although some treatments have been proposed and tried with little success. Treatment such as gene therapy, enzyme replacement therapy (ERT) and bone marrow transplantation (BMT) have been attempted even in young dogs but so far they have proved unable to be effective in reaching the very protected cells of the central nervous system. Ultimately, preventing puppies from inheriting Gangliosidosis by DNA Disease Screening parents is the best method available.

References

GM1 gangliosidosis: Review of clinical, molecular, and therapeutic aspects. Nicola Brunetti-Pierria, Fernando Scaglia
GM1-gangliosidosis in Alaskan Huskies: Clinical and Pathologic Findings. G. Muller, S. Alldinger, A. Moritz, A. Zurbriggen, N. Kirchhof, A. Sewell, W. Baumgartner
Image Credit – University of Arizona – https://disorders.eyes.arizona.edu/disorders/gm1-gangliosidosis
Muller G, Baumgartner W, Moritz A, Sewell A, Kustermannkuhn B (1998). Biochemical findings in a breeding colony of Alaskan huskies suffering from GM(1)-gangliosidosis. Journal of Inherited Metabolic Disease 21: 430-431
Saunders GK, Wood PA, Myers RK, Shell LG, Carithers R. GM1 gangliosidosis in Portuguese water dogs: pathologic and biochemical findings. Vet Pathol. 1988 Jul;25(4):265-9
Shell LG, Potthoff AI, Carithers R, Katherman A, Saunders GK, Wood PA, Giger U. (1989) Neuronal-visceral GM1 gangliosidosis in Portuguese water dogs. Journal of Veterinary Internal Medicine. 3(1):1-7
Storage Disorders. K. G. Braund
Wang ZH, Zeng B, Shibuya H, Johnson GS, Alroy J, Pastores GM, Raghavan S, Kolodny EH. Isolation and characterization of the normal canine beta-galactosidase gene and its mutation in a dog model of GM1-gangliosidosis. J Inherit Metab Dis. 23 (2000) 593-606