GM1 - gangliosidosis 1

Gangiliosidosis is a severe inherited storage disease of dogs characterized by various neurological symptoms.

In dogs, two types of gangliosidosis have been described:

• Gangliosidosis 1:  β-galactosidase deficiency - Portuguese Water Dog, Alaskan Malamute, Shiba
• Gangliosidosis 2: acid β-hexosaminidase deficiency - Toy Poodle, Golden Retriever

The GM1 in Portuguese water dogs is caused by mutation c.179G>A in the GLB1 gene affecting the beta-galactosidase synthesis. The deficiency of a functional enzyme leads to storage of gangliosides in the central nervous system, peripheral nerves and kidneys. The presence of abnormal constituents in the urine is typical for this disease.

The first clinical signs become apparent from 5-6 months of age. The affected dogs suffer from asymmetric growth and progressive neurological degradation caused by incorrect function of cerebellum. The first symptoms are loss of weight and "wide-based" gait.  Subsequently, progressive loss of coordination, muscle tremors and muscle ataxia occur. The eyes of the dog can be also affected, beginning with squinting and ending by complete loss of vision. The progressive worsening of the health condition results in premature death of the dog or euthanasia.

GM1 in Portuguese water dog is an autosomal recessive disorder. The disease affects dogs with P/P (positive / positive) genotype only. Dogs with P/N (positive /negative) genotype are clinically without any symptoms. They are genetically considered carriers of the disease (heterozygotes). In offspring of two heterozygous animals following genotype distribution can be expected: 25 % N/N (healthy non-carriers), 25 % P/P (affected), and 50 % N/P (healthy carriers). Because of high risk of producing affected offspring, mating of two N/P animals (carriers) can not be recommended.

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References:

Z. H. Wang, B. Zeng, H. Shibuya, G. S. Johnson, J. Alroy, G. M. Pastores, S. Raghavan, E. H. Kolodny: Isolation and characterization of the normal canine β-galactosidase gene and its mutation in a dog model of GM1-gangliosidosis; Journal of Inherited Metabolic Disease September 2000, Volume 23, Issue 6, pp 593-606