Genetic basis - Gangliosidosis GM2 in Shiba Inu dogs is caused by a homozygous 3-base pair deletion mutation (c.849_851delCCT) in the HEXB gene, which encodes the beta subunit of the hexosaminidase enzyme complex. This deletion results in a defective beta-hexosaminidase enzyme and causes Sandhoff disease, a subtype of GM2 gangliosidosis. The condition is inherited in an autosomal recessive manner, meaning affected dogs have two copies of the mutation, while carriers have one copy without showing symptoms.
Pathophysiology - Due to defective beta-hexosaminidase, GM2 gangliosides accumulate in lysosomes, particularly in neurons of the central nervous system. This excessive storage causes progressive neuronal damage, leading to lysosomal storage disease symptoms involving neurological deterioration, including ataxia, tremors, and cognitive decline. The condition shows similarities to human Sandhoff disease.
Complications - Progressive ataxia and loss of coordination. Head tremors and muscle stiffness. Vision impairment and reduced menace response. Behavioral changes and neurological decline. Affected dogs generally succumb or are euthanized by 18 to 23 months of age due to severe neurological impairment and poor quality of life.
Why This Matters to Breeders and Vets - This fatal neurodegenerative disease significantly impacts Shiba Inu welfare. Breeders benefit from genetic screening programs to eliminate the disease. Veterinarians play a key role in early diagnosis, client education, supportive care, and advocating for responsible breeding to minimize the disease burden in Shiba Inus
