Gangliosidosis is a type of lysosomal storage disease, caused by an inherited error in how lipid (fat) is metabolised within cells. Cats with GM2 gangliosidosis lack the beta-hexosaminidase enzyme that is needed to metabolise, or break down certain lipids, and this causes certain lipid molecules to build up inside cells because they cannot be excreted. Eventually this interferes with normal processes in the cell, and the cell cannot perform its normal functions anymore.
Two types of gangliosidosis are seen in cats, called GM1 gangliosidosis, which is seen in the Korat, Siamese (and Siamese related breeds) and domestic cat, and GM2 gangliosidosis, seen in the Korat, Burmese and domestic cat. GM2 Gangliosidosis causes gangliosides ( lipid-carbohydrate molecules derived from cell membranes) to build up in the cells of the central nervous system (the brain) and leads to neurologic signs in affected cats. This disease is inherited as autosomal recessive trait, meaning for a cat to be affected she must inherit a defective gene from each of her parents. Cats with only one copy of the affected gene are not affected, but are carriers of the disease and can pass the trait on to future generations. In humans GM2 gangliosidosis is also known as Tay-Sachs disease.
Cats with GM2 gangliosidosis are affected at a young age, usually between 4-6 weeks of age, and will generally be severely affected and require euthanasia by around 6-8 months of age. The signs are progressive, from weakness in the legs, a fine head tremor and weight loss, to a wobbly gait and other gait abnormalities such as frequent falling, and finally to depression, difficulty eating and drinking, a more severe tremor and even seizures. Affected kittens may have stunted growth, and there may also be clouding of the eyes and vision problems.
There is no cure for GM2 gangliosidosis, but genetic testing is available so that carrier animals may be detected. The only way to manage the disease is prevention by avoiding breeding carrier animals. Genetic diversity can be maintained by breeding carrier animals that have otherwise valuable traits to known "clear" animals, and only breeding with their tested "clear" kittens.