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Alaskan Husky Encephalopathy (AHE)
| Acronym: | AHE |
| Gene: | SLC19A3 |
| Mutation: | c.624delinsTGCAA |
| Inheritance: | Autosomal recessive |
| Sample type: | Cheek Swab, Whole Blood (EDTA) |
Genetics and characteristics
Alaskan Husky Encephalopathy (AHE) is an inherited neurological disorder affecting Alaskan Huskies. In 1992, a novel degenerative disorder of the central nervous system of juvenile Alaskan Huskies has been recognized. Until 1998, extensive examinations of affected dogs have been conducted and the disorder has been recognized as Alaskan Husky encephalopathy (AHE). It is caused by a mutation in the thiamine transporter 2 (SLC19A3) gene. AHE has been previously suggested as a mitochondrial encephalopathy, based on similarities shared with human Leigh Syndrome (LS). A similar disorder to Alaskan Husky encephalopathy has been described in European Yorkshire terriers, but an underlying cause has not been identified.
Thiamine is also known as thiamin or vitamin B1. It is a vitamin of B complex and a water-soluble essential vitamin. It has an important role in the metabolism of carbohydrates in all cells and for the proper function of the nervous system and a critical role in mitochondrial metabolism. This makes thiamin an essential nutrient. The central nervous system is dependent on mitochondria for energy metabolism, and thiamine plays an important role in mitochondrial metabolism. Therefore, thiamine deficiency can cause severe neurological disorders. It is supposed that thiamine deficiency (TD) causes bilaterally symmetrical brain lesions in animals and people. Classical histological lesion of TD in dogs is described as bilaterally symmetrical polioencephalomalacia, confined to the brain stem nuclei, periventricular grey matter, claustrum, cerebellar modulus, lateral geniculate nuclei, caudal colliculi, occipital and parietal cortex. It has been observed that dogs with thiamine deficiency and AHE-affected dogs histologically have the same lesions of bilaterally symmetrical encephalomalacia, while anatomic patterns of lesion distribution are distinctively different. The difference is that AHE-affected dogs do not have lesions localized in the caudal colliculus or lateral geniculate nucleus and TD-affected dogs do not have thalamic lesions. It is suspected that AHE is due to a localized TD, while global TD in AHE dogs is unlikely.
Alaskan Husky encephalopathy (AHE) symptoms usually develop in juvenile time, between 6 months of age. Symptoms appear suddenly, although in some dogs a chronic history has been documented. Since the disorder includes multiple parts of the brain, clinical signs are various, such as seizures, high stepping gait, trouble walking and eating, and central blindness. AHE-affected dogs most often are euthanized due to poor quality of life. One dog lived for 1 year after the onset of symptoms and died of natural causes, as was documented. As previously mentioned, AHE is caused by a mutation in the SLC19A3 gene that encodes for thiamine transport protein. The SLC19A3 gene belongs to a group of genes known as solute carrier family 19 (SLC19) that transports water-soluble vitamins into cells. Alaskan Husky Encephalopathy (AHE) is inherited in an autosomal recessive pattern. Healthy parents of an affected puppy are obligate heterozygotes and therefore carry one mutant allele. Heterozygotes have no symptoms. Dogs homozygous for the mutation will display the symptoms of the AHE. At conception, each cub has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
Results Reported As
Test Result |
Interpretation of test result |
CLEAR |
Tested mutation was not detected in animal with „clear“ result. Animal tested as clear has wild-type allele in homozygous state (i.e. two pairs of healthy alleles). It will not develop disease caused by tested mutation.* It will pass only wild-type allele to its offspring. |
CARRIER |
Tested mutation was detected in animal with „carrier“ result. Animal tested as carrier has one wild-type and one mutation allele, it is in heterozygous state. It will not develop disease caused by tested mutation.* It can pass wild-type or mutation allele to its offspring. |
AFFECTED |
Tested mutation was detected in animal with „affected“ result. Animal tested as affected has two copies of mutation alleles affecting the gene. It is likely the animal will experience a genetic disorder due to this mutation.** It will pass only mutation allele to its offspring. |
*Test excludes only tested mutation but not possible unknown mutations or factors that can lead to similar condition/symptoms.
** Potential unknown mutations or multiple other factors can possibly affect the likelihood of experiencing a genetic disorder.
References:
Vernau KM, Runstadler JA, Brown EA, Cameron JM, Huson HJ, 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. doi:10.1371/journal.pone.0057195
Brenner O, Wakshlag JJ, Summers BA, de Lahunta A. Alaskan Husky Encephalopathy – A canine neurodegenerative disorder resembling subacute necrotizing encephalomyelopathy (Leigh Syndrome). Acta Neuropathol. 2000 Jul;100(1):50-62.