GM2 Gangliosidosis Poodle Type
GM2 Gangliosidosis Poodle Type is a congenital lysosomal disorder affecting the Poodle dog breed and it is known as GM2 gangliosidosis varant 0. It is a progressive neurodegenerative disorder with a fatal outcome. GM2 belongs in a group of lysosomal disorders known as gangliosidosis, caused by the accumulation of lipids known as gangliosides. In the gangliosidoses group of disorders, other than GM2, belongs another disorder type, known as GM1. There are three variants of GM2 gangliosidosis, 0, B and AB. Gangliosidosis variant 0 (GM2) has a human equivalent, known as Sandhoff disease, while in animals, GM2 has been identified in dogs, cats, pigs, deer and flamingos.
GM2 gangliosidoses is a result of beta-hexosaminidase (Hex) deficiency, an enzyme that catalyzes the biodegradation of lipids gangliosides. This hydrolytic enzyme can be found in lysosomes. Hex is composed of two main isoenzymes, Hex A and Hex B, while only Hex A acts as the GM2 activator protein. Defects in the genes encoding for named proteins causes their improper function. In case of unfunctioning beta-hexosaminidase enzyme, gangliosides start to accumulate, especially in the lysosomes of neurons, causing problems.
Symptoms start to occur in the affected dog around 9 to 12 months of age. Neurological symptoms include stiff gait, loss of balance, falling ataxia, intention tremor, postural deficit, astasia, decreased menace response, vision defect or loss, decreased corneal reflex, and decreased level of consciousness. In most of affected dogs another symptom was vomiting, without known reason. Common finding in affected Toy Poodles was diffuse T2-hyperintensity of the subcortical white matter in the cerebrum, caused by hypoplasia of the myelin or delayed myelination, or both.
In general, clinical signs of GM2 Poodle Type are similar to those recognized previously in a Golden Retriever with GM2, with same age of symptom onset. Main noticed difference between GM2 Poodle type and Golden Retriever type was loss of pupillary light reflexes, which was not recorded in Poodles.
The GM2 is progressive, and disorder usually ends fatal, with death onset between 18 to 23 months of age.
GM2 Gangliosidosis Poodle Type is caused by deleterious mutations in the HEXB gene. HEXB gene is encoding β-subunit of lysosomal enzyme β –N-acetylhexosaminidase. GM2 is inherited as an autosomal recessive disorder. Healthy parents of an affected puppy are obligate heterozygotes, and therefore carry one mutant allele. Heterozygotes have no symptoms. Dogs homozygous for the mutation will display the symptoms of the amelogenesis imperfecta. At conception, when mating two carrier dogs, each cub has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
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Tamura S, Tamura Y, Uchida K, Nibe K, Nakaichi M, Hossain MA, Chang HS, Rahman MM, Yabuki A, Yamato O. GM2 gangliosidosis variant 0 (Sandhoff-like disease) in a family of toy poodles. J Vet Intern Med. 2010 Sep-Oct; 24(5):1013-9.