Cerebellar Abiotrophy (CA)

Cerebellar abiotrophy is a hereditary neurodegenerative disorder. Progressive neurodegeneration of Purkinje cells in the cerebellum leads to the gradual loss of neurons. The remaining Purkinje cells are small and exhibit significant morphological abnormalities. The disease has been described primarily in Arabian horses. At a low frequency, it also occurs in Danish Sport Horses, Bashkir horses, Trakehner horses, and Welsh ponies.

The first signs usually appear between approximately six weeks and four months of age. Affected animals may exhibit ataxia, intention tremors of the head, a reduced or completely absent response to potential danger, a wide-based stance, impaired coordination of movements, and impaired perception of body position and overall body movement. Affected horses are easily startled. They may also fall and subsequently have difficulty getting back to their feet.

The disease is characterized by variable expression. The degree and severity of clinical signs may differ between individuals. Some affected horses show relatively mild signs, while others may develop much more severe symptoms. The disease is not fatal, and a horse may continue to live and function with the resulting disability. Unfortunately, however, its hyperreactive, sensitive, and unpredictable behavior can make it considerably dangerous to its surroundings.

The disease is associated with the substitution mutation g.13122415C>T, located in exon 4 of the TOE1 gene. The MUTYH gene, which is located near TOE1, is affected by the regulatory influence of this mutation. MUTYH expression is particularly strong in the cerebellum and Purkinje cells. Reduced expression results in decreased protection against oxidative DNA damage.

Cerebellar abiotrophy (CA) is an autosomal recessive hereditary disorder. The disease therefore develops in individuals that inherit the mutated allele from both parents. These individuals are designated P/P (positive/positive). Carriers of the mutated allele, designated N/P (negative/positive), inherit the mutation from only one parent and do not show clinical signs. However, they can pass the mutation on to their offspring.

When two heterozygous carriers (N/P) are mated, theoretically 25% of the offspring will be genetically clear, 50% will be carriers, and 25% will inherit two copies of the mutation and be affected by CA.

A mating between a clear individual (N/N) and a carrier (N/P) theoretically produces 50% carriers and 50% clear offspring.

If a carrier (N/P) is mated with an affected individual (P/P), theoretically 50% of the offspring will be affected and 50% will be carriers.

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References:

Brault, Leah S., Thomas R. Famula, and M. Cecilia T. Penedo. "Inheritance of cerebellar abiotrophy in Arabians." American Journal of Veterinary Research 72.7 (2011): 940–944.

Brault, Leah S., et al. "Mapping of equine cerebellar abiotrophy to ECA2 and identification of a potential causative mutation affecting expression of MUTYH." Genomics 97.2 (2011): 121–129.

Brault, L. S., and M. C. T. Penedo. "The frequency of the equine cerebellar abiotrophy mutation in non-Arabian horse breeds." Equine Veterinary Journal 43.6 (2011): 727–731.

Primo, A. L. M., et al. "Cerebellar abiotrophy in a quarter horse foal." Journal of Equine Veterinary Science 147 (2025): 105386.