Test Detail

GM2 gangliosidosis is a hereditary lysosomal disease of the Burmese cat in which a deficiency in the GM2 ganglioside degradation pathway causes toxic accumulation in the central nervous system. It affects the brain and, to a lesser extent, other organs. Affected cats develop progressive juvenile neurological deterioration leading to death within the first years. It is a disease with no curative treatment and with exclusively genetic control.

Test targeted at the Burmese. It is a rare disease within the breed and there are no systematically published carrier frequencies: limited data.

- Juvenile onset of head tremor and ataxia\n- Progressive neurological deterioration with loss of balance\n- Apathy, disorientation and difficulty eating\n- Possible corneal opacity and coarse facial features\n- Death from neurological deterioration in infancy or youth

GM2 gangliosidosis in the Burmese cat was biochemically characterised as a defect of the beta subunit of hexosaminidase (HEXB) and the cat became established as a model of human GM2. Bradbury and colleagues (2009) identified the causal variant in the European Burmese: a deletion in intron 11 that generates aberrant, non-functional transcripts. The specific test was incorporated into the breed's breeding panels.

- Test Burmese breeding dogs before mating: it identifies clear and carrier animals.\n- Do not mate two carriers with each other.\n- A carrier can be mated to a clear cat with no risk of affected cats; test the offspring that remain in breeding.\n- Request the variant interpretation guide from the laboratory to document the pedigree.

Differential diagnosis with other juvenile neurodegenerative diseases of the cat (GM1, mucopolysaccharidoses, leukoencephalopathies) and with intoxications. Enzyme studies and MRI can guide clinical cases; the DNA test confirms. In the event of an affected cat, review the status of both parents and of the littermates.

1. Bradbury AM et al. 2009. Neurodegenerative lysosomal storage disease in European Burmese cats with hexosaminidase beta-subunit deficiency. Mol Genet Metab. PMID: 19231264
2. Martin DR et al. 2004. An inversion of 25 base pairs causes feline GM2 gangliosidosis variant. Exp Neurol. PMID: 15081585
3. Kanae Y et al. 2007. Nonsense mutation of feline beta-hexosaminidase beta-subunit (HEXB) gene causing Sandhoff disease. Res Vet Sci. PMID: 16872651
4. Yamato O et al. 2008. Retrospective diagnosis of feline GM2 gangliosidosis variant 0 (Sandhoff-like disease) in Japan. J Vet Med Sci. PMID: 18772556
5. OMIA:001462-9685.