Encephalopathy, necrotising

 

Gene: SLC19A3

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: 

Alaskan Husky mutation: Insertion, plus substitution, SLC19A3 gene; c.624 ins.TTGC, c625 C>A, p(Q208H fs STOP 13), exon2

Yorkshire Terrier mutation: Insertion, deletion, SLC19A3 gene; c.205_210 del.6 nt, ins.35 nt, p.(P69I fs STOP 45)

Medical system: Neurological

Breeds: Alaskan Husky, Yorkshire Terrier

Age of onset of symptoms: Between 6 months and 2 years

Necrotizing encephalopathy is a neurological disease caused by a genetic defect in the production of a protein essential for vitamin B1 transport. This defect causes neuronal death, and the central nervous system is the main area affected by the disease. Clinical signs, either acute or chronic, include convulsions, altered wakefulness, dysphagia, absence of threat response, general blindness, hypermetria, peripheral limb proprioception failures, facial hypoalgesia, ataxia and tetraparesis. In addition, affected animals may have reduced sensitivity to facial pain, as well as difficulty in eating and swallowing. Behavioral changes may also occur. Progression of the disease is variable, and may occur in stages. Most dogs will die of complications or be euthanized for humane reasons.

 

References:

OMIA link: [1097-9615]

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]

Thorsrud JA, Huson HJ. (2021) Description of breed ancestry and genetic health traits in arctic sled dog breeds. Canine Med Genet 8:8. [pubmed/34544496]

Drögemüller M, Letko A, Matiasek K, et.al. (2020) SLC19A3 loss-of-function variant in Yorkshire terriers with Leigh-like subacute necrotizing encephalopathy. Genes (Basel) 11:1215. [pubmed/33081289]

Verneau K, Napoli E, Wong S et al. (2015) Thiamine deficiency-mediated brain mitochondrial pathology in Alaskan Huskies with mutation in SLC19A3.1.  Brain Pathology. 25(4):441-453. [pubmed/25117056]

Vernau KM, Runstadler JA, brown EA et al. (2013) Genome-wide association analysis identifies a mutation in the Thiamine Transporter 2 (SLC19A3) gene associated with Alaskan Husky Encephalopathy. PLoS One. 8(3):e57195. [pubmed/23469184]

Brenner O, Wakshlag JJ, Summers BA, de Lahunta A. (2000) Alaskan Husky Encephalopathy – A canine neurodegenerative disorder resembling subacute necrotizing encephalomyelopathy (Leigh Syndrome). Acta Neuropathol. 100(1):50-62. [pubmed/10912920]

 

Contributed by: Emma Quiniou and Tommy Hamelin-Labrecque, class of 2027, Veterinary Medicine Faculty, University of Montreal.  (Translation: DWS).