Genetic basis - GM2 gangliosidosis (variant 0 or Sandhoff disease) in Poodles is caused by a frameshift mutation in the HEXB gene, specifically a deletion mutation (c.283delG) that results in a premature stop codon and loss of function of the beta-hexosaminidase B enzyme. This mutation causes deficiency in both hexosaminidase A and B activities. The disease is inherited in an autosomal recessive manner, meaning affected dogs inherit two copies of the mutant gene while carriers have one copy without symptoms.
Pathophysiology - The deficiency of beta-hexosaminidase A and B enzymes leads to accumulation of GM2 gangliosides within lysosomes of neurons and other cells. This storage causes progressive neuronal damage, demyelination, and brain atrophy. The pathological changes result in clinical neurological deterioration including motor dysfunction, ataxia, tremors, and seizures
Complications - Progressive cerebellar ataxia (loss of coordination). Muscle tremors and weakness. Difficulty walking and behavioral changes. Neurological decline leading to inability to eat or move properly. Death or euthanasia usually occurs within months after onset due to severe neurological impairment.
Why This Matters to Breeders and Vets - GM2 gangliosidosis is a severe, progressive, and fatal neurodegenerative disease affecting Poodles. Genetic screening supports informed breeding decisions for prevention. Veterinarians benefit from awareness of this condition for early diagnosis and client counseling. Both breeders and vets play vital roles in improving welfare and reducing the burden of inherited diseases in the breed through education and genetic testing