Mucopolysaccharidosis I, MPSI (Hurler)

 

Gene: IDUA

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:

Plott Hound mutation: Substitution, IDUA gene; c.155+1 G>A, splicing error

Boston Terrier mutation: Insertion, IDUA gene; c.19_20 ins CGGCCCCC, p.(R7P fs)

Golden Retriever mutation: Deletion, IDUA gene; c.1400-76_1521+89 del, p.G467_E507 del)

Medical system: Metabolic, lysosomal storage disease

Breeds: Boston Terrier, Golden Retriever, Plott Hound

Age of onset of symptoms: Around the age of 4 to 6 months

Mucopolysaccharidosis I (Hurler syndrome) is a lysosomal storage disease. Affected animals are deficient in an enzyme named alpha-L iduronidase whose function is to break down glycosaminoglycans (GAGs, also called mucopolysaccharides).  GAGs are normal tissue components found in the extracellular space of connective tissue.  In mucopolysaccharidosis I there is a build-up of particular GAGs within the tissues of the body.  By 4 to 6 months of age, affected puppies start showing signs of growth retardation, bone deformities, pain on handling, progressive lameness and corneal clouding leading to visual impairment.  The disease is progressive and affected animals are either euthanized or die as a result of complications before the age of 2 to 3 years.

 

References:

OMIA link: [0664-9615]

Nenninger A, Ben-Shlomo G, Allbaugh R, et al. (2023) Clinical and pathological characterization of ophthalmic disease in a canine model of mucopolysaccharidosis type I. J Inherit Metab Dis 46(2):348-357.  [pubmed/36601751]

Faller KME, Ridyard AE, Gutierrez-Quintana R, et al. (2020) A deletion of IDUA exon 10 in a family of Golden Retriever dogs with an attenuated form of mucopolysaccharidosis type I. J Vet Intern Med 34:1813-1824.  [pubmed/32785987]

Mansour TA, Woolard, KD, Vernau, KL, et al. (2020) Whole genome sequencing for mutation discovery in a single case of lysosomal storage disease (MPS type 1) in the dog. Sci Rep 10:6558.  [pubmed/32300136]

Menon KP, Tieu PT, Neufeld EF. (1992) Architecture of the canine IDUA gene and mutation underlying canine mucopolysaccharidosis 1. Genomics 14(3):763-768. [pubmed/1339393]