Mucopolysaccharidosis IIIA in Dachshunds

Mucopolysaccharidosis is a hereditary lysosomal storage disease in which mucopolysaccharides (glycosaminoglycans - dermatan, heparan and chondroitin sulphate) accumulate in lysosomes. While other types of mucopolysaccharidosis manifest with somatic symptoms such as facial dysmorphic features, corneal opacity, bone lesions, lack of body growth relative to the head and joint problems, type III is suppressed and presents mainly with severe central nervous system involvement.

The cause of the disease in Dachshunds is the c.740_742delCCA mutation in the gene for heparan sulfate sulfamidase (SGSH). Deficiency in the activity of this enzyme results in the accumulation of heparan sulfate in the lysosomes.

The mode of inheritance of the mutation is autosomal recessive. This means that only individuals who inherit the mutated gene from both parents will develop the disease. Carriers of the mutated gene are clinically healthy but pass the mutation on to their offspring. In the case of a mating between two heterozygous individuals, theoretically 25% of the offspring will be completely healthy, 50% of the offspring will be carriers and 25% of the offspring will inherit the mutated gene from both parents and will therefore be affected by the disease.

The genetic test can clearly reveal the genotype of the animal and is a useful tool for breeders to prevent unintentional breeding of affected puppies.

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References:

Aronovich, E.L., Carmichael, K.P., Morizono, H., Koutlas, I.G., Deanching, M., Hoganson, G., Fischer, A., Whitley, C.B.: Canine heparan sulfate sulfamidase and the molecular pathology underlying Sanfilippo syndrome type A in Dachshunds Genomics 68:80-84, 2000. Pubmed reference: 10950929