Genetic basis - GM1 Gangliosidosis is caused by a 19-base pair duplication mutation in exon 15 of the GLB1 gene encoding beta-galactosidase enzyme in Alaskan Huskies. This mutation disrupts a potential exon splicing enhancer causing exon skipping and production of truncated, nonfunctional beta-galactosidase proteins. The disease is inherited in an autosomal recessive manner, meaning dogs must inherit two copies of the mutated gene (one from each parent) to develop the condition.
Pathophysiology - Beta-galactosidase deficiency leads to accumulation of GM1 ganglioside in lysosomes of cells throughout the body, especially in the brain and nervous system. Accumulation causes progressive neuronal cell death, demyelination, and widespread dysfunction in the central nervous system. Histologically, affected neurons show vacuolation and storage material accumulation impairing neuronal function.
Complications - Clinical signs appear between 5 to 8 weeks of age, including vision loss, head tremors, ataxia (loss of coordination), weakness, and lethargy. Disease progression is rapid and fatal. Neurological deterioration leads to blindness, paralysis, and severe disability.
Why This Matters to Breeders and Vets - For breeders, avoiding affected matings prevents production of puppies with a devastating, lethal neurodegenerative disorder, improving breed welfare. Veterinarians aid in early diagnosis, managing clinical signs, and advising breeders about genetic risks. Understanding the autosomal recessive inheritance allows informed breeding decisions and supports breed health management. Early testing and breeding control help reduce prevalence and improve overall breed wellbeing.