Lethal neurometabolic encephalopathy described in the husky, caused by a mutation of the SLC19A3.1 gene, which encodes the thiamine transporter THTR2 predominantly expressed in the central nervous system. The defect produces a local thiamine deficiency in the brain and, secondarily, mitochondrial dysfunction and oxidative stress, with bilateral symmetrical lesions in the thalamus, cortex and brainstem. Clinically it is multifocal, progressive and with a fatal course.

Affected breeds: historically, sled husky (Alaskan husky); commercial tests also offer it for the Siberian Husky. The mutation was not detected in 187 dogs of 51 breeds other than husky. The true carrier frequency in the Siberian Husky is not reliably published; cases are concentrated in North American sledding lines.

- Progressive ataxia\n- Epileptic seizures\n- Altered mental state and decreased level of consciousness\n- Proprioceptive deficit and tetraparesis\n- Central blindness and dysphagia\n- Subacute and progressive course until death or euthanasia

AHE was described in sled huskies (Alaskan husky) due to its neuropathological similarity to human Leigh disease. In 2013, Vernau and colleagues performed a GWAS in eight cases and twenty related controls and located an interval on CFA25 containing the SLC19A3 gene, which in the dog is duplicated into two paralogues. Only SLC19A3.1 is expressed in brain, cerebellum and spinal cord, and it showed a 4-bp insertion and a SNP in exon 2 (c.624insTTGC, c.625C>A) that truncates 279 amino acids of the transcript. Subsequent biochemical studies confirmed a deficiency of thiamine pyrophosphate-dependent enzymes and increased oxidative stress in the brain.

- Test breeding animals with the SLC19A3 test before mating\n- Do not mate two carriers: 25% risk of affected homozygotes\n- A carrier may be mated with a clear dog; offspring intended for breeding must be tested\n- Exclude affected animals and their known carrier parents from breeding\n- Consider the variable response to thiamine and biotin supplementation as a palliative tool, not as a substitute for genetic prevention

Differential diagnosis with other mitochondrial encephalopathies and with Leigh disease. MRI shows bilateral symmetrical lesions in the thalamus, brainstem and, in some cases, basal ganglia. The canine SLC19A3 mutation is the first animal model of human SLC19A3 encephalopathies (thiamine metabolism dysfunction syndrome 2 / biotin-thiamine-responsive basal ganglia disease). Note: the term AHE traditionally refers to the Alaskan husky (sled dog), not to the Siberian Husky as a pure breed; the test is offered to both populations.

1. Vernau KM 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:e57195. PMID: 23469184
2. Vernau K et al. (2015) Thiamine deficiency-mediated brain mitochondrial pathology in Alaskan Huskies with mutation in SLC19A3.1. Brain Pathol 25:441-453. PMID: 25117056