Lysosomal storage disease due to acid beta-galactosidase deficiency, which causes accumulation of GM1 gangliosides in the central nervous system and in various organs. It produces a progressive neurodegeneration of early onset with ataxia, cerebellar signs and weakness, and is lethal in the first months/years of life. It is inherited in an autosomal recessive manner and is associated with mutations in the GLB1 gene, which differ by breed.

Breeds with a variant documented in OMIA: Portuguese Water Dog, Shiba Inu, Alaskan Husky, Beagle and English Springer Spaniel (the latter two with other GLB1 variants). In the Shiba Inu the carrier frequency described in Japan is around 1-3 % (Uddin 2013); outside the breeds of origin the data are limited.

- Onset between 6 and 8 weeks, evident by around 7 months\n- Ataxia, wide-based gait, decreased proprioception\n- Intention head tremor, hypermetria and dysmetria\n- Internal strabismus and positional nystagmus\n- Limb weakness and weight loss\n- Proportionate dwarfism in some breeds

Canine GM1 gangliosidosis was first recognised in the Portuguese Water Dog and the Shiba Inu as biochemical models of the human disease. Wang and colleagues (2000) identified in the Portuguese Water Dog a G→A transition in exon 2 of GLB1 that changes arginine to histidine (R60H). Yamato and colleagues (2002) described in the Shiba Inu a deletion of a cytosine in exon 15 that generates a premature stop codon. In sled huskies a 19-bp duplication in exon 15 that alters mRNA splicing was also documented. Each finding made it possible to develop breed-specific genetic tests.

- Test breeding animals with the GLB1 test specific to their breed\n- Do not mate two carriers: 25 % risk of lethal affected homozygotes\n- A carrier may be mated to a clear animal; offspring intended for breeding must be tested\n- In the Shiba Inu, prioritise screening of Japanese lines with a higher described frequency\n- Exclude affected animals from breeding

Differential diagnosis with other neurodegenerative lysosomal storage diseases of the young (GM2/Sandhoff, fucosidosis, leukodystrophies) and with hereditary cerebellar ataxias. Measurement of beta-galactosidase activity in leukocytes and the genetic test are confirmatory. In the Shiba Inu, GM2 (HEXB) coexists, so in the face of a compatible picture both tests should be requested.

1. Wang ZH et al. 2000. Isolation and characterization of the normal canine beta-galactosidase gene and its mutation in a dog model of GM1-gangliosidosis. J Inherit Metab Dis. PMID: 11032334
2. Yamato O et al. 2002. A novel mutation in the gene for canine acid beta-galactosidase that causes GM1-gangliosidosis in Shiba dogs. J Inherit Metab Dis. PMID: 12555949
3. Kreutzer R et al. 2005. A duplication in the canine beta-galactosidase gene GLB1 causes exon skipping and GM1-gangliosidosis in Alaskan huskies. Genetics. PMID: 15944348
4. Uddin MM et al. 2013. Molecular epidemiology of canine GM1 gangliosidosis in the Shiba Inu breed in Japan. BMC Vet Res. PMID: 23819787
5. Wang P et al. 2018. Canine GM2-Gangliosidosis Sandhoff Disease Associated with a 3-Base Pair Deletion in the HEXB Gene. J Vet Intern Med. PMID: 29106755
6. OMIA:000402-9615.