Test Detail

GM1 and GM2 gangliosidoses are hereditary lysosomal diseases of the cat in which gangliosides accumulate in the nervous system due to a deficiency of degrading enzymes. GM1 is due to beta-galactosidase deficiency and GM2 to alterations of the hexosaminidase system (including its activator protein). The progressive accumulation in neurons causes severe and irreversible neurological deterioration: head tremor, ataxia and loss of autonomy leading to death in the first years of life. There is no curative treatment, so control is based on avoiding matings between carriers.

Described and validated in the Siamese, Korat and Japanese domestic cat. The test is also offered in breeds derived from the Siamese (Balinese, Javanese, Oriental Shorthair, Peterbald, Seychellois, Thai, Tonkinese), although they are not included in OMIA for these variants: limited data. Carrier frequencies vary between populations and few countries publish systematic data.

- Head and limb tremor appearing in young cats
- Progressive ataxia (clumsiness, falls, irregular gait)
- Increasing neurological deficit: apathy, loss of responsiveness, difficulty eating
- Corneal opacity in some cases
- Seizure episodes in advanced stages
- Death from neurological deterioration, generally before 2-3 years of age

Feline gangliosidoses were described clinicopathologically in the 1970s and 1980s, with cases in Siamese cats and in other populations, and were characterized as lysosomal enzyme defects by ganglioside biochemistry. Studies in cats also gained scientific relevance because they served as an animal model of human gangliosidoses for testing therapies. The identification of the specific mutations (GLB1 for GM1 and genes of the hexosaminidase system for GM2) allowed the development of DNA tests applied to breeding control. The combined GM1/GM2 test was incorporated into feline panels to cover both forms at once in breeds of the Siamese group and the Korat.

- Test breeding animals before the first mating: it distinguishes clear, carrier and affected animals.
- Never breed two carriers together: 25% of the litter would be affected.
- A valuable carrier may be bred to a clear animal; test the offspring intended for breeding.
- Record the results in the pedigree to contain the silent spread of the allele in breeds derived from the Siamese.

Differential diagnosis with other storage diseases (mucopolysaccharidoses, leukodystrophies), intoxications and infectious diseases of the CNS in young cats. Enzyme study in leukocytes or fibroblast culture and ganglioside determination can support the diagnosis when the clinical picture does not match the test. In the event of a confirmed case, report the status of the parents and siblings for the whole litter.

1. Martin DR et al. 2008. Molecular consequences of the pathogenic mutation in feline GM1 gangliosidosis. Mol Genet Metab. PMID: 18353697
2. Ueno H et al. 2016. GM1 gangliosidosis in a Japanese domestic cat: a new variant identified in Hokkaido, Japan. J Vet Med Sci. PMID: 26234889
3. Uddin MM et al. 2013. Identification of Bangladeshi domestic cats with GM1 gangliosidosis caused by the c.1448G>C mutation of the feline GLB1 gene. J Vet Med Sci. PMID: 23123943
4. Bradbury AM et al. 2009. Neurodegenerative lysosomal storage disease in European Burmese cats with hexosaminidase beta-subunit deficiency. Mol Genet Metab. PMID: 19231264
5. Martin DR et al. 2004. An inversion of 25 base pairs causes feline GM2 gangliosidosis variant. Exp Neurol. PMID: 15081585
6. Kanae Y et al. 2007. Nonsense mutation of feline beta-hexosaminidase beta-subunit (HEXB) gene causing Sandhoff disease. Res Vet Sci. PMID: 16872651
7. Beecy SJ et al. 2025. Clinical and biochemical abnormalities in a feline model of GM2 activator deficiency. Mol Genet Metab. PMID: 39644670
8. OMIA:000402-9685 / OMIA:001462-9685.