Mucopolysaccharidosis VI (MPS6) – Cat (2 variants)

Mucopolysaccharidosis (MPS) is a group of genetic disorders that often lead to serious brain and developmental problems. One type, called MPS VI (MPS6), is caused by two copies of a mutated ARSB gene. This test looks for two specific forms of MPS VI: a milder version (MPSVIm; D520N) and a more severe one (MPSVIs; L476P). Both are inherited in an autosomal recessive pattern.

The mild form of MPS VI (MPSVIm; D520N) is commonly found in some cat breeds, especially Siamese, but it also occurs in non-Siamese cats. On its own, this mild variant does not cause health problems. However, cats that inherit both the mild and severe forms (MPSVIm and MPSVIs) can develop serious joint disease as they age, although they usually don't show other symptoms.

Cats with two copies of the severe form (MPSVIs ; L476P) may show signs as early as 3 to 6 weeks old. These include abnormal bone development, wide faces with short noses and small ears, stiff necks and lower backs, and slower growth compared to healthy siblings. Before 8 months of age, they may develop weakness or paralysis in the back legs due to spinal cord compression. X-rays reveal overall bone thinning, rough bone texture, and severe spine joint damage, including irregular bone surfaces and bone spurs. Some may also display vision loss due to retinal degeneration.

Since the severe variant (L476P) is linked to disease, it should be carefully monitored in cat breeds, especially those with Siamese ancestry. In contrast, there is no evidence that the mild variant (D520N) causes any health problems. Testing for D520N is only useful when the severe variant is also tested, to avoid breeding cats with both mutations (compound heterozygotes), which can lead to serious joint disease.

Although some breeders have raised concerns about possible health effects of the D520N variant, no link has been proven. It is safe to breed cats that carry or are affected by the mild variant (D520N) as long as they do not also carry the severe variant (L476P). Excluding these cats from breeding can unnecessarily reduce genetic diversity, increasing the risk of inbreeding and related health issues. Therefore, results for the D520N variant alone should not be used to make breeding decisions.

More information about breeding decisions for cats affected by MPS VI can be found in, among other sources, the article Mucopolysaccharidosis VI in cats – clarification regarding genetic testing by Leslie Lyons et al. (2016).

Pubmed ID: 8910299 (1996); 9421472 (1998); 27370326 (2016)

Omia ID: 666