Genetic basis of GM2 Gangliosidosis (Korat Type) - is an autosomal recessive lysosomal storage disease caused by a frameshift mutation (cytosine deletion at c.39delC) in the HEXB gene, which encodes the beta subunit of hexosaminidase. Cats must inherit two copies of the mutant allele to show clinical disease. Carrier cats (one mutant copy) are asymptomatic but can pass the mutation to offspring. The test for the Korat GM2 mutation specifically detects this variant and does not identify other HEXB mutations seen in other breeds.
Pathophysiology - The defective HEXB gene leads to insufficient beta-hexosaminidase enzyme activity. This enzyme normally breaks down GM2 gangliosides (glycolipids) in nerve cells. When the enzyme is deficient, GM2 gangliosides accumulate, causing progressive damage and dysfunction of neurons throughout the central and peripheral nervous systems. Clinical onset starts as early as 4 weeks of age, rapidly advancing to severe neurological impairment and degeneration.
Complications - Korat kittens affected by GM2 gangliosidosis show: Fine head tremors and unsteady movements early in life (from 4 weeks). Progressive ataxia, loss of coordination, inability to walk or stand. Dysmetria (impaired movement control). Neurological deterioration: blindness, seizures, loss of motor function. Rapid deterioration leads to death, usually before 8 months of age.
Why This Matters to Breeders and Vets - Genetic Screening: Carrier detection allows breeders to avoid mating two carriers, preventing affected litters (25% risk for each carrier × carrier mating). Health Management: Early identification helps veterinarians diagnose neurological decline in young cats, informs humane care decisions, and avoids prolonged suffering. Breed-Specific Testing: The Korat HEXB mutation is unique to Korats and requires precise genetic testing not applicable to other feline breeds. Breed Preservation: Widespread carrier screening supports healthy breed management and protection of Korat genetic diversity without perpetuating this lethal disorder.
Summary - GM2 Gangliosidosis (Korat Type) results from a frameshift deletion in the HEXB gene, causing failure to break down GM2 gangliosides and rapid neurodegeneration in affected kittens. Lethal before 8 months, the disease can be prevented by carrier screening and careful breeding practices. Routine genetic testing is essential for Korat breeders and veterinarians to ensure animal welfare and breed health.