Gangliosidosis (AB variant) in Domestic cat

Gangliosidosis GM2 type AB is also known as Tay-Sachs disease. It is a lysosomal storage disease in which gangliosides accumulate in the lysosomes of neurons due to a deficiency of the activator protein G(M2). The accumulation of gangliosides leads to a fatal impairment of central nervous system function. Clinical manifestations are evident from about 14 months of age and include head and hind limb tremors, unsteady gait including sudden falls and increased startle response to sharp sounds. Late symptoms of the disease include loss of mobility, blindness and epileptic seizures.

The disease is caused by mutation c.516_519del in the GM2A gene, which encodes the ganglioside activator GM2 required for successful degradation of the ganglioside G(M2)A.

The mode of inheritance of the mutation is autosomal recessive. This means that only individuals who inherit the mutated gene from both parents will develop the disease. Carriers of the mutated gene are clinically healthy but pass the mutation on to their offspring. In the case of a mating between two heterozygous individuals, theoretically 25% of the offspring will be completely healthy, 50% of the offspring will be carriers and 25% of the offspring will inherit the mutated gene from both parents and will therefore be affected by the disease.

The genetic test can clearly reveal the genotype of the animal and is a useful tool for breeders to prevent unintentional breeding of affected kittens.

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References:

Martin, DR., Cox, NR., Morrison, NE., Kennamer, DM., Peck, SL., Dodson, AN., Gentry, AS., Griffin, B., Rolsma, MD., Baker, HJ. : Mutation of the GM2 activator protein in a feline model of GM2 gangliosidosis. Acta Neuropathol (Berl) 110:443-50, 2005. Pubmed reference: 16200419