Mucopolysaccharidosis IIIa, MPSIIIA

 

Gene: SGSH

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:

Dachshund mutation: Deletion, SGSH gene; c.740_742 del.CCA, p.(T247del)

New Zealand Huntaway mutation: Insertion, SGSH gene; c.685_686 ins.A, p.(Y229 STOP)

Medical system: Metabolic, neurological, lysosomal storage disease

Breeds: Dachshund Miniature Longhair/Shorthair, Dachshund Miniature Wirehair, Dachshund Standard Longhair/Shorthair, Dachshund Standard Wirehair, New Zealand Huntaway

Age of onset of symptoms: Around the age of 3 years

Mucopolysaccharidosis IIIa (Dachshund type, Huntaway type) is a hereditary lysosomal storage disease.  There is a deficiency of the enzyme heparan-N-sulfatase, resulting in an accumulation of heparin sulfate in cells.  In Dachshunds and the New Zealand Huntaway dog, this leads to a progressive neurological disease.  Symptoms first appear around the age of 3 years and include ataxia, loss of reflexes (especially at the hind legs), tremors of the head, swaying and abnormal eye movements.  Although the progression of symptoms is relatively slow, affected animals are often euthanized within a year or so of showing signs due to quality of life issues.

 

References:

OMIA link:  [1309-9615]

Donner J, Freyer J, Davison S, et al. (2023) Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs.  PLoS Genet. 19(2):e1010651. [pubmed/36848397]

Story BD, Miller ME, Bradbury AM, et al. (2020) Canine models of inherited musculoskeletal and neurodegenerative diseases. Front Vet Sci 7:80. [pubmed/32219101]

Winner LK, Marshall NR, Jolly RD, et al. (2019) Evaluation of disease lesions in the developing canine MPS IIIA brain. JIMD Rep 43:91-101.  [pubmed/29923090]

Yogalingam G, Pollard T, Gliddon B Jolly RD, Hopwood JJ. (2002) Identification of a mutation causing mucopolysaccharidosis Type IIIA in New Zealand Huntaway Dogs. Genomics 79(2):150-153. [pubmed/11829484]

Aronovich EL, Paige Carmichael KP, Morizono H, Koutlas IG, et al. (2000) Canine heparin sulphate sulfamidase and the molecular pathology underlying Sanfilippo Syndrome Type A in Dachshunds. Genetics 68:80-84. [pubmed/10950929]

Fischer A, Carmichael KP, Munnell JF, et al. (1998) Sulfamidase deficiency in a family of Dachshunds: A canine model of mucopolysaccharidosis IIIA (Sanfilippo A). Pediatr Res. 44(1):74–82. [pubmed/9667374]