Gangliosidosis is an inherited inborn error of lipid metabolism, also known as a ‘lysosomal storage disease’.
Affected cats lack an enzyme required to metabolise certain lipids (fats) which means that they accumulate within cells in the body, causing disruption to normal cellular function.
Two forms of gangliosidosis are recognised in cats:
- GM1 – caused by a lack of the enzyme acid β galactosidase
- GM2 – caused by a lack of the enzymes hexosaminidase A and B
The disease causes an accumulation of lipids known as gangliosides, particularly in neuronal cells in the central nervous system. Affected cats develop progressive neurological signs such as:
- Ataxia (uncoordinated gait)
- Dysmetria (high-stepping gait)
- Nystagmus (involuntary side-to-side movement of the eyes)
Other signs that may be seen include:
- Neutrophils and lymphocytes (white blood cells) may contain cytoplasmic granules
- The liver may sometime become enlarged
- There may be facial dysmorphism – flat broad head and small skull
- There may be clouding of the cornea and visual impairment
- Affected kittens may be stunted
In affected cats, signs are usually first evident by the time kittens are 1-5 months of age, and will progress over time to the point where there will be weakness (first of the hind limbs then front limbs as well), depression, seizures and eventually the kittens will die, typically at 8-10 months of age.
Genetic defect and testing for gangliosidosis
Both GM1 and GM2 gangliosidosis are inherited in a simple autosomal recessive manner. Affected cats are homozygous (have two copies of the defective gene), whereas cats with one copy of the defective gene are asymptomatic carriers.
The cause of GM1 gangliosidosis has been identified as a defect in the GLB1 gene, while GM2 gangliosidosis is caused by defects in the HEXB gene.
DNA tests are available to detect both carrier and affected cats with both forms of gangliosidosis.
Cats that have been identified with gangliosidosis include: