GM1 gangliosidosis is a lysosomal deposition disease that causes the accumulation of GM1 gangliosides in various tissues, characterized by progressive neuromuscular dysfunction and growth impairment. The genetic variant responsible is found in the GLB1 gene, which encodes the enzyme beta-galactosidase, essential for ganglioside degradation.
Symptoms
Clinical signs usually appear between 3 and 4 months of age in the form of mild tremors of the head or limbs. Eventually, affected cats have difficulty walking in a coordinated manner and may experience blindness and epileptiform seizures towards the end of the disease at around 9 to 10 months of age.
Disease Management
There is currently no effective treatment for feline GM1 gangliosidosis. However, gene therapy based on intravenous injection with an adeno-associated viral vector (AAV) is under investigation. The efficacy of intravenous treatment with AAV9 has been demonstrated and has improved the quality of life and prolonged survival of treated cats without severe manifestations of toxicity.
Genetic basis
This disease follows an autosomal recessive mode of inheritance. Autosomal recessive inheritance means that the cat, regardless of sex, must receive two copies of the mutation or pathogenic variant to be at risk of developing the disease. Both parents of an affected cat must carry at least one copy of the mutation. Animals with only one copy of the mutation are not at increased risk of developing the disease, but may pass the mutation on to future generations. Breeding between cats carrying genetic variants that may cause disease, even if they do not show symptoms, is not recommended.
Technical report
GM1 gangliosidosis is a lysosomal neurodegenerative disease in which the accumulation of GM1 gangliosides (glycolipid) occurs in various tissues. The disease arises as a consequence of alteration of the GLB1 gene encoding beta-galactosidase, a lysosomal enzyme crucial for the degradation of gangliosides such as GM1. In cats affected by gangliosidosis, a variant in this gene has been identified that consists of a base substitution (c.1448G>C). This change prevents the correct localization of the β-galactosidase protein in lysosomes, resulting in the abnormal accumulation of GM1 ganglioside in the central nervous system.
Most affected breeds
Japanese domestic
Korat
Siamese
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