Lysosomal storage disorder due to beta-hexosaminidase deficiency that causes accumulation of GM2 gangliosides in the nervous system. The most frequent form in the dog is variant 0 (Sandhoff), due to variants in HEXB that affect hexosaminidase A and B; in the Japanese Chin a Tay-Sachs-like form (type I / variant B) due to variants in HEXA has been described. It produces progressive neurodegeneration of juvenile onset with a lethal course. It is inherited in an autosomal recessive manner.

Breeds with a documented variant: Toy Poodle (HEXB; the allele is rare in the population, Rahman 2012), Shiba Inu (HEXB; rare but distributed variant, Kolicheski 2017 and Wang 2018) and Japanese Chin (HEXA c.967G>A; identified in two related dogs, Sanders 2013). Limited data on reliable frequencies outside these series.

- Onset between 9 and 12 months
- Falls, head tremor, ataxia and apparent blindness
- Stiff gait, loss of balance, difficulty walking
- Vacuoles or granules in the cytoplasm of lymphocytes and CSF cells
- Cerebral and cerebellar atrophy with white matter involvement on MRI
- Progressive lethal course

Canine GM2 was initially described in Toy Poodles with ataxia, tremor and blindness of onset around 9 months and death around 18-23 months. Rahman and colleagues (2012) identified in the Toy Poodle the deletion in HEXB that defines the Sandhoff variant. In the Shiba Inu, Kolicheski (2017) and Wang (2018) described an in-frame deletion in HEXB. In the Japanese Chin, Sanders and colleagues (2013) identified a missense variant in HEXA, which constitutes a Tay-Sachs-like form.

- Test breeding animals with the breed-specific test (HEXB in Toy Poodle and Shiba Inu; HEXA in Japanese Chin depending on the laboratory)
- Do not mate two carriers: 25% risk of lethal affected homozygotes
- A carrier can be mated with a free animal; offspring intended for breeding must be tested
- In the Shiba Inu, also consider the GM1 test (GLB1) because both diseases coexist
- Exclude affected animals from breeding

Differential diagnosis with GM1 (GLB1) of the Shiba, almost clinically indistinguishable, and with other neurodegenerations of the young. The hexosaminidase A and B activity assay in plasma/leukocytes gives an indication of the variant (Sandhoff vs Tay-Sachs), but confirmation is molecular. MRI shows cerebral and cerebellar atrophy with white matter involvement.

1. Rahman MM et al. (2012) A frameshift mutation in the canine HEXB gene in toy poodles with GM2 gangliosidosis variant 0 (Sandhoff disease). Vet J 194(3):412-416. PMID: 22766310
2. Kolicheski AL et al. (2017) GM2 gangliosidosis in Shiba Inu dogs with an in-frame deletion in HEXB. J Vet Intern Med 31(5):1520-1526. PMID: 28833537
3. Wang P et al. (2018) Canine GM2-gangliosidosis Sandhoff disease associated with a 3-base pair deletion in the HEXB gene. J Vet Intern Med 32(1):340-347. PMID: 29106755
4. Sanders DN et al. (2013) GM2 gangliosidosis associated with a HEXA missense mutation in Japanese Chin dogs: a potential model for Tay Sachs disease. Mol Genet Metab 108(1):70-75. PMID: 23266199