Juvenile subacute necrotising encephalopathy of the Yorkshire Terrier, neuropathologically very similar to human Leigh disease and to husky encephalopathy. It produces progressive neurological signs in dogs under one year of age, with bilateral symmetrical lesions in the thalamus, brainstem and other structures. It is inherited in an autosomal recessive manner and is associated with an indel variant in the SLC19A3 gene, which encodes the thiamine transporter THTR2.

Affected breed: Yorkshire Terrier. No reliable large-scale carrier frequencies are published; cases are sporadic but the breed is the predisposed one (ten affected animals in a single series).

- Progressive ataxia in dogs under one year of age
- Central visual deficits
- Epileptic seizures
- Decreased mental state
- Subacute course progressing to death or euthanasia
- Bilateral symmetrical necrotic lesions in thalamus and brainstem

Described by Sawashima in 1996 and neuropathologically characterised by Baiker and colleagues in 2009, without finding defects in the mitochondrial genome. In 2020, Drögemüller and colleagues applied homozygosity mapping and whole-genome sequencing to ten cases: they found a single private indel in exon 2 of SLC19A3, c.205_210delins35 (p.Pro69Ilefs*45), after filtering against 729 control genomes (including 60 breed controls). The variant co-segregated with the phenotype in the 172 genotyped Yorkshire Terriers and truncates 86% of the protein. It is the second SLC19A3 alteration described in dogs after the husky one.

- Test breeding animals with the SLC19A3 test (Yorkshire variant) before mating
- Do not mate two carriers: 25% risk of affected homozygotes
- A carrier may be mated to a clear animal; offspring intended for breeding must be tested
- Exclude affected animals and known carriers from breeding
- Do not confuse with the husky test (another SLC19A3 variant)

Differential diagnosis with husky encephalopathy (another SLC19A3 variant), other mitochondrial encephalopathies and communicating hydrocephalus. MRI shows bilateral symmetrical lesions in thalamus and brainstem; histology reproduces features of human Leigh disease. The response to thiamine/biotin is variable and does not replace genetic prevention.

1. Drögemüller M et al. 2020, SLC19A3 loss-of-function variant in Yorkshire Terriers with Leigh-like subacute necrotizing encephalopathy. Genes (Basel) 11(10):1215. PMID: 33081289. 2. Baiker K et al. 2009, Leigh-like subacute necrotising encephalopathy in Yorkshire Terriers: neuropathological characterisation, respiratory chain activities and mitochondrial DNA. Acta Neuropathol. PMID: 19466433. 3. Sawashima Y et al. 1996, Clinical and pathological findings of a Yorkshire terrier affected with necrotizing encephalitis. J Vet Med Sci. PMID: 8844603.