Genetic basis - Gangliosidosis GM2 (B variant, also known as Tay-Sachs disease in humans) in Japanese Chin dogs is caused by a missense mutation in the HEXA gene, specifically the c.967G>A transition mutation resulting in a p.E323K amino acid substitution. This mutation disrupts the catalytic function of the hexosaminidase A enzyme. The disease is inherited as an autosomal recessive trait, requiring two copies of the defective gene for clinical signs to develop
Pathophysiology - The deficiency of the hexosaminidase A enzyme leads to accumulation of GM2 gangliosides in neurons. This buildup causes progressive lysosomal storage, neuronal dysfunction, and degeneration, particularly in the central nervous system. This results in neurological signs such as ataxia, tremors, and loss of coordination, ultimately leading to severe neurological decline
Complications - Progressive cerebellar ataxia and difficulty walking. Vision deficits and mental dullness. Head tremors and altered mental status. Seizures in some cases. Disease progression leads to severe neurological impairment and death or euthanasia generally within months after symptom onset (often by 18-23 months old).
Why This Matters to Breeders and Vets - GM2 gangliosidosis severely affects Japanese Chin health and welfare due to fatal progressive neurological decline. Breeders benefit from genetic screening to make informed decisions, minimizing affected puppies. Veterinarians play a crucial role in early diagnosis, managing clinical signs, advising clients on prognosis, and emphasizing the importance of genetic testing to reduce disease frequency in future generations
