Neurological conditions

Lysosomal storage diseases:

Gangliosidosis GM1
Gangliosidosis GM1 is an autosomal recessively inherited lysosomal storage disease (see under general section). The condition is due to a lack of the enzyme acid β galactosidase which leads to a build up of GM1 ganglioside within cells, particularly of the nervous system, as gangliosides are required for formation of neuronal cell membranes. Clinical signs are seen from an early age, typically 2-5 months, and may often initially be mistaken for cerebellar hypoplasia (which is a condition caused by infection with Feline Panleukopenia Virus), this is because kittens are ataxic (uncoordinated walking) and dysmetric (high-stepping walking) with the presence of a tremor and nystagmus (rapid sideways movement of the eyes). However, unlike cerebellar hypoplasia, in which the signs are present at birth and remain stable, signs associated with gangliosidosis progress as the kitten ages. Kittens are likely to be stunted, and do not eat well. In some cases the liver may feel enlarged, and facial dysmorphism may be present (i.e. the kittens have a flat broad head and small ears). Vision may be poor, and the cornea (clear front part of the eyes) may appear cloudy. Signs gradually progress to paraplegia (weakness of the hindlimbs) or tetraplegia (weakness of all limbs), with altered mentation (depression, dementia, seizures, aggression), and ultimately terminate in death at a young age.
Diagnosis may be suspected on clinical signs, presence of small vacuoles within lymphocytes (white blood cells) and the presence of oligosaccharides in urine. Confirmation may be made by identifying the enzyme deficiency in brain or liver tissue, in skin cells (fibroblasts) or in white blood cells. The genetic defect causing this disease in Korat cats has been identified as a single nucleotide substitution in the GLB1 gene. This enabled detection of carrier status by nucleotide sequencing techniques. An initial survey suggested that this condition was not present in the UK, but was seen most commonly in the United States. However, it was also present in other countries within Europe. With importation of animals into the UK there is always the potential that carriers of this disease may be introduced.

Gangliosidosis GM2
Gangliosidosis GM2 is also an autosomal recessively inherited lysosomal storage disease. There are 4 major enzyme deficiencies associated with GM2 in humans, but in Korat cats the condition has been identified as being due to a lack of hexosaminidase A and B, thereby resembling the condition in humans called Sandhoff’s disease. The genetic defect is a cytosine deletion in the HEXB gene, which is different from the 25-base deletion in the HEXB gene that has been identified to cause GM2 in domestic longhair cats. As with GM1, clinical signs are seen from an early age (1-3 months), and progression of the disease may be more rapid than for GM1. Neutrophils and lymphocytes (white blood cells) may contain cytoplasmic granules which stain dark blue and light blue respectively. Again, the previous study did not detect the presence of GM2 in Korat cats in the UK.
Recently, a PCR test has been identified which can detect the various forms of gangliosidosis. Although not yet commercially available, this test should be more rapid and less costly than the currently available molecular techniques to detect the genetic abnormalities. This test has been developed by the Scott-Ritchey Research Centre, College of Veterinary Medicine, Auburn University AL 36849, which is where the molecular diagnostic tests were also developed.
Both GCCF and FIFe have a registration rule that Korat cats registered as suitable for breeding must be proved clear of GM1 and GM2.

Baker H.J, Smith B.F, Martin D.R and Foureman P. (2001) Molecular Diagnosis of Gangliosidosis: A Model for Elimination of Inherited Diseases in Pure Breeds In: Consultations in Feline Internal Medicine 4 Ed. J.R. August W.B. Saunders, Philadelphia pp 615-620
De Maria R, Divari S, Bo S et al. Beta-galactosidase deficiency in a Korat cat: a new form of feline GM1-gangliosidosis. Acta Neuropath 1998 96 (3) 307-14
Neuwelt EA, Johnson WG, Blank NK et al. (1985) Characterisation of a new model of GM2 gangliosidosis (Sandhoff’s Disease) in Korat cats. J Clin Invest  76 482-490
Chi-Young J and Smith BF. (2007)  Development of quantitative polymerase chain reaction assay for allelic discrimination of gangliosidosis in cats. Am J Vet Res  68 231-235
Muldoon LL, Neuwelt EA, Pagel MA and Weiss DL. (1994) Characterisation of the molecular defect in a feline model for type II GM2-gangliosidosis (Sanfhoff disease). Am J Pathol  144(5) 1109-18

Useful Websites
www.upenn.edu/research/centers/penngen/services/metaboliclab - urine screening for oligosaccharides can be done through this laboratory
www.koratworld.com/gm - for frther information regarding GM1 and GM2 in Korat cats