Neuronal Ceroid Lipofuscinosis 4A, NCL4A

 

Gene: ARSG

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.

Mutation: Substitution, ARSG gene; c.296 G>A, p.(R99H)

Medical systems: Neurologic, lysosomal storage disease

Breeds: American Bulldog, American Pit Bull Terrier, American Staffordshire Terrier/Amstaff, Border Collie, Boston Terrier, Boxer, Bull Terrier, Bull Terrier-Miniature, English Bulldog, Labrador Retriever, Rhodesian Ridgeback

Age of onset of symptoms: Around the age of 3 to 5 years

The Neuronal Ceroid Lipofuscinoses are a family of hereditary neurodegenerative diseases.  Neuronal Ceroid Lipofuscinosis 4A (NCL4A), also called Batten disease, is a lysosomal storage disease that affects terriers of the Pit Bull and Staffordshire Terrier types.  Affected individuals have an enzyme defect that blocks normal metabolism resulting in an accumulation of metabolic waste within cells.  Nerve cells are particularly sensitive to this defect.  Affected animals develop progressive neurological symptoms around the age of 3 to 5 years, including muscle incoordination, tremors, abnormal eye movements, abnormal gait and balance problems.  Affected animals are most often euthanized 2 to 4 years after the initial appearance of clinical signs.

 

References:

OMIA link: [1503-9615]

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]

Stee K, Van Poucke M, Lowrie M, et al. (2023) Phenotypic and genetic aspects of hereditary ataxia in dogs. J Vet Intern Med. [pubmed/37341581]

Cerda-Gonzalez S, Packer RA, Garosi L, et al. (2021) International veterinary canine dyskinesia task force ECVN consensus statement: Terminology and classification. J Vet Intern Med 35:1218-1230.  [pubmed/33769611]

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

Abitbol M, Thibaud JL, Olby NJ Hitte C, et al. (2010) A canine Arylsulfatase G (ARSG) mutation leading to a sulfatase deficiency is associated with neuronal ceroid lipofuscinosis. PNAS 107(33):14775-14780. [pubmed/20679209]