Awareness Of Lafora Disease In Miniature Wirehaired Dachshunds Could Aid Prevention



Miniature Wirehaired Dachshund breeder Dianne Graham of Pulaski, Virginia, learned about Lafora disease five years ago when she discovered an English dog in her dog’s pedigree was affected. Two of her bitches tested as carriers of the autosomal recessive condition that was first recognized in Mini Wirehairs in the U.K. more than three decades ago. Graham quickly realized that few U.S. breeders knew about Lafora. 

A late-onset progressive myoclonic epilepsy seen in dogs around 7 years of age, Lafora disease at its peak in 2013 affected up to 10 percent of Miniature Wirehaired Dachshunds in the U.K. and 42 percent were carriers. Gradually, after a genetic test became available in 2012 to owners and breeders, disease incidence began to decrease. In 2017, only 3 percent of Mini Wirehairs in the U.K. were affected and 26 percent were deemed carriers.  

Graham made it her mission to educate North American breeders about the incurable condition that eventually claims the lives of all affected dogs. She began a database to record the testing results of North American Miniature Wirehaired Dachshunds and investigated the history of affected dogs in America. 

Family of Mini Wirehairs Shares Lafora

A different scenario took place in Miniature Wirehaired Dachshunds in the U.K., where for decades before the gene mutation for Lafora disease was discovered, breeders had produced litters in which some dogs later in life showed signs of epilepsy. They suspected it was a hereditary condition, though the late onset of clinical signs meant that most dogs had already been bred when it became apparent they were affected. 

In the 1990s, veterinary neurologists Clare Rusbridge, BVMS, PhD, DipECVN, FRCVS, of the University of Surrey in Guildford, England, and Sue Fitzmaurice, BVSc, MRCVS, DACVIM (Neurology), of The Ralph Veterinary Referral Centre in Marlow, Buckinghamshire, England, found an extended family of Miniature Wirehairs in which the disease was clearly inherited. 

They sent pedigree information and DNA from those dogs to researchers in Canada who were studying a similar inherited disease in humans. The researchers identified the Epm2b gene mutation for Lafora disease in the Mini Wirehairs in 2005 and matched it to the human Lafora disease mutations in the EPM2A gene and the EPM2B gene. Affected dogs, as well as affected people, inherit two copies of the gene mutation. The Epm2b gene mutation in dogs results in the intracellular accumulation of abnormal glycogen phosphatase laforin, a protein essential for making normal structured glycogen. 

Affected dogs are not able to convert starch into sugar, so insoluble glycogen builds up in their cells into large accumulations called Lafora bodies. The mutation disables the gene from controlling laforin and from protecting tissue against carbohydrate accumulation. As the Lafora bodies gradually grow, they have a neurotoxic effect in the central nervous system. Lafora disease appears as progressive myoclonic epilepsy, but it is actually a glycogen metabolism disorder.   

Graham, who had two bitches test as carriers, says, "I won't breed to an outside dog unless I study the pedigree. It has been a hard road to eliminate this from my line. I finally have a male that tested clear. Every affected dog is someone's much-loved pet, and they may have to live with the epileptic fits associated with Lafora disease for six to 10 years. That's a hard price to pay when you consider how easy it is to screen dogs prior to breeding."