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 (mild): Substitution, ARSB gene; c.1558 G>A, p.(D520N)

Medical systems: Metabolic, skeletal

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.  The disease is caused by a deficiency in the enzyme Arylsulfatase B, which results in an accumulation of dematan sulfate in tissues and a spill-over of dermatan sulfate into the urine.  Symptoms can be severe or mild depending on the specific mutation, and double heterozygote animals can show symptoms.  Severe symptoms include growth retardation, abnormal facial shape, bone and cartilage deformities, and joint degeneration.  Mild symptoms include joint mobility problems, and may not be diagnosed until adulthood.

 

References:

OMIA link: [0666-9685]

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]