Mucopolysaccharidosis VI (MPS VI)

 

Gene: ARSB

Transmission: Autosomal recessive

For an autosomal recessive genetic disease, an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease, but are carrier animals that can pass the mutation on to future generations.

Mutations:

Siamese mutation 1 (severe): Substitution, ARSB gene; c.1427 T>C, p.(L476P)

Siamese mutation 2 (non-symptomatic, modifier to mutation 1): Substitution, ARSB gene; c.1558 G>A, p.(D520N)

Medical systems: Metabolic, skeletal, lysosomal storage disease

Breeds: Abyssinian, American Curl, Balinese, Bengal, Birman, Chausie, Colorpoint Shorthair, Domestic Cat, Donskoy, European Shorthair, Havana Brown, Highland Lynx, Lykoi, Maine Coon, Ocicat, Oriental Longhair, Oriental Shorthair, Ragdoll, Russian Blue, Savannah, Siamese, Singapura, Somali, Tonkinese

Age of onset of symptoms: Variable

Mucopolysaccharidosis VI (MPS VI) is a genetic disease seen in the Siamese breed.  It is considered a lysosomal storage disease, caused by a deficiency in the lysosomal enzyme Arylsulfatase B resulting in an accumulation of dematan sulfate in tissues and a spill-over of dermatan sulfate into the urine.  Symptoms from the L476P mutation (mutation 1) can be early and severe, including growth retardation, abnormal facial shape, bone and cartilage deformities, and joint degeneration.  The L476P mutation, if present, should be selected against.  The D520N mutation (mutation 2) does not cause disease by itself but can have a modifying influence in the presence of the L476P mutation resulting in mild symptoms of joint disease in adult cats.  The D520N (modifying) mutation can have a high incidence in several cat breeds, but should not be the focus of genetic selection by itself, to avoid the deleterious effects of inbreeding.

 

References:

OMIA link: [0666-9685]

Boeykens F, Abitbol M, Anderson H, et al. (2024) Development and validation of animal variant classification guidelines to objectively evaluate genetic variant pathogenicity in domestic animals. Front Vet Sci 11:1497817.  [pm/39703406]

Anderson H, Davison S, Lytle KM, et al. (2022) Genetic epidemiology of blood type, disease and trait variants, and genome-wide genetic diversity in over 11,000 domestic cats.  PLoS Genet. 16;18(6):e1009804.  [pubmed/35709088]

Bravaccini B, Buffagni V, Negro L, et al. (2022) Mucopolysaccharidosis VI in a European Shorthair cat: Neurological presentation, computed tomography findings and genetic investigation. Acta Vet Hung [pubmed/36037045]

Lyons LA, Grahn RA, Genova F, et al. (2016) Mucopolysaccharidosis VI in cats – clarification regarding genetic testing. BMC Vet Res 12:136. [pubmed/27370326]

Sewell AC, Haskins ME, Giger U. (2012) Dried blood spots for the enzymatic diagnosis of lysosomal storage diseases in dogs and cats. Vet Clin Pathol 41:548-57, 2012. [pubmed/23121383]

Lischka FW, Gomez G, Yee KK, et al. (2008) Altered olfactory epithelial structure and function in feline models of mucopolysaccharidoses I and VI. J Comp Neurol 511:360-72, 2008. [pubmed/18803239]

Sleeper MM, Kusiak CM, Shofer FS, O’Donnell P, et al. (2008) Clinical characterization of cardiovascular abnormalities associated with feline mucopolysaccharidosis I and VI. J Inherit Metab Dis 31:424-31, 2008. [pubmed/18509743]

Crawley AC, Muntz FH, Haskins ME, et al. (2003) Prevalence of mucopolysaccharidosis type VI mutations in Siamese cats. J Vet Intern Med 17(4):495-498. [pubmed/12892300]

Crawley AC, Yogalingam G, Muller VJ, et al. (1998) Two mutations within a feline mucopolysaccharidosis type VI colony cause three different clinical phenotypes. J. Clin. Invest. 101(1):109-119. [pubmed/9421472]

Yogalingam G, Litjens T, Bielicki J, et al. (1996) Feline mucopolysaccharidosis Type VI. Characterization of recombinant N-acetylgalactosamine 4-sulfatase and identification of a mutation causing the disease. Journal of Biological Chemistry 271(44):27259-27265. [pubmed/8910299]

Haskins ME, Aguirre GD, Jezyk PF, Patterson DF. (1980) The pathology of the feline model of mucopolysaccharidosis VI. Am J Pathol. 101(3):657-74. [pubmed/6778219]