Retinopathy with vitamin E deficiency (RVED) plus ataxia (TTPA-related)

Gene: TTPA

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.

Mutation: Deletion, TTPA gene: c.23_124 del., p.(Pro8_Pro48 del., Pro8>Arg), exon1, Chr.29.

Medical system: Ocular, neurological

Breed: English Cocker Spaniel

Age of onset of symptoms: Variable, from 3 to 6 years of age.

Vitamin E deficiency is characterised by a clinical syndrome of ocular problems, including retinal degeneration and visual defects, as well as neurological signs including ataxia and muscle weakness. It can be the result of dietary deficits (environmental causes) or it can be hereditary (genetic defects).

Hereditary vitamin E deficiency has been historically reported in several dog breeds, mention the English Cocker Spaniel. English Cocker Spaniel dogs exhibiting progressive ocular defects with or without hindlimb proprioceptive deficits and ataxia were examined clinically.  Blood levels of alpha-tocopherol (vitamin E) were found to be very low.  Molecular studies identified a deletion in the TTPA gene as being tightly associated with the phenotype.  The TTPA gene codes for a carrier protein for alpha tocopherol.  A population survey of 186 English Cocker Spaniels revealed a carrier frequency of 14%.  Dietary vitamin E supplementation was found useful in slowing or stopping the progression of neurological signs in affected animals but could not reverse ocular defects.  A DNA test is available and will allow breeders and veterinarians to eliminate this disease from the English Cocker Spaniel breed.  Elimination of the causal mutation must be done prudently so as not to cause further hereditary problems due to genetic bottlenecks.  Whether or not the TTPA mutation is the cause of hereditary vitamin E deficiencies in other dog breeds has not been reported.

References:

OMIA link: [2922-9615]

Oliver JAC, Stanbury K, Schofield E et al. (2025) A TTPA deletion is associated with Retinopathy with Vitamin E Deficiency (RVED) in the English Cocker Spaniel Dog. G3 (Bethesda) 15:jkaf016.  [pm/39874248]

McLellan GJ, Bedford PG. (2012) Oral vitamin E absorption in English Cocker Spaniels with familial vitamin E deficiency and retinal pigment epithelial dystrophy. Vet Ophthalmol 15 Suppl 2:48-56.  [pm/22831287]

McLellan GJ, Cappello R, Mayhew IG, et al. (2003) Clinical and pathological observations in English cocker spaniels with primary metabolic vitamin E deficiency and retinal pigment epithelial dystrophy. Vet Rec 153:287-92. [pm/14509574]

With contributions by: Kayla Kulisek and Laura Tinmouth, Class of 2030, Faculty of Veterinary Medicine, University of Montreal.  (Translation: DWS).