HAVE YOU HEARD OF LAFORA’S DISEASE ?

This account of a programme of research into a (human) childhood disease does not appear at first sight to be of relevance to our breed club newsletter, but as well as being of great interest it will quickly commend itself to be something of which all Dachshund people should be aware, and lend their support where appropriate. Originally prepared by Committee member Laura Sexton for the Wirehaired club magazine, it is included here at her request in the interest of making as many people as possible know of the present situation, at the earliest possible date . Show it to your friends, doggy or otherwise, and to your Vet to add to his or her knowledge.

~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~

Could your twitching dog be the clue to curing a deadly childhood disease ?

Most of you reading the title of this article will probably frown their eyebrows, but please read on, because your dog could be able to provide the clue needed to treat a terrible neurologic disease that strikes children down hard, in the prime of their lives.

Two experienced veterinary neurologists, Dr. Susan Fitzmaurice and Dr. Clare Rusbridge have been confronted in the last few years with Miniature Wirehaired Dachshunds having epileptic seizures after the age of 7. The fits were provoked by flashing lights, watching television or if approached in sunlight. Sue and Clare went to great lengths to establish a diagnosis for these dogs and with the help of two veterinary pathologists (Dr. Diane Shelton, San Diego, California, and Dr. Robin Franklin, Cambridge, England) they came to the conclusion that this disease was the same as the deadly human disease, Lafora’s Progressive Myoclonus Epilepsy. Fortunately, the disease in the dogs is much less severe than its human counterpart.

My name is Berge Minassian, I am a paediatric neurologist and scientist dedicated to understanding, and hopefully one day curing this devastating condition. This disease, in humans, strikes otherwise completely normal children, just as they are entering adolescence. Once the fits start, they do not stop, despite our best efforts. The seizures get worse and worse until they kill the child. Because of the onset of the disease after 10 years of age, many of the families, not knowing what is brewing in their first child, have had further children, who witness the ordeal of their sibling, only to themselves then starting to succumb to the condition. Our research laboratory is part of the large Center for Applied Genomics at the Hospital for Sick Children in Toronto, Canada and is headed by Dr. Stephen Scherer. This is the same lab which was involved in such seminal discoveries as the gene for Cystic Fibrosis. We have already discovered one gene for Lafora's disease. Surprisingly, we also discovered that in humans, there is a second gene, which also causes this horrible disease. This second Lafora's disease gene has been very hard to find in humans. We now know that this second Lafora's disease gene is the same gene causing the problem in the Miniature Wirehaired Dachshunds. If we can find the Dachshund Lafora gene, then that would be a major leap forward in unravelling the biology of this disease in humans. We would be much closer to a fuller understanding of what is going on, and hence much closer to a potential cure for our children.

We are planning no experiments of any kind on the dogs. What we need is a little bit of blood, that is all. If you have a Miniature Wirehaired Dachshund who has fits, then please contact us, and allow your puppy to give us a little bit of blood. Epilepsy is common in dogs, and there are many forms of epilepsy. Please contact us only if your dog is a miniature wirehaired dachshund. Many children in the future will look back at this and will be eternally grateful Dr. Susan Fitzmaurice (in Woking) and Dr Clare Rusbridge (in Wimbledon) will be in charge of the blood collection in the UK. All reasonable costs will be covered by our research funds. Their addresses are on the next page.. Any of you can contact me any time, and I will do what I can to answer your questions, and help coordinate this effort. My full address is below.

Finally, do remember that the disease is much milder in the dogs. The dogs have an altogether normal life apart from the fits later as they age.

Thank you wholeheartedly, Berge.

Berge A. Minassian MD CM, FRCP(C)

Asst Professor of Pediatrics

Div of Neurology, Hospital for Sick Children

555 University Ave. Toronto, Ontario, M5G 1X8 Canada.

Phone :0416-813 6291 Fax:0416-813 6334

email: bminass@sickkids.ca

Myoclonic Epilepsy (Lafora’s disease)

in Miniature Wirehaired Dachshunds.

Recently a degenerative neurological disease called Lafora’s disease has been identified in miniature wirehaired dachshunds. The disease is characterised by myoconus. Typically this looks like a backwards shuddering/jerking of the head when there is movement towards the eyes, when light intensity increases, when there is flickering light (e.g. television) or at sudden noises. Some dogs also develop epilepsy. Middle aged to older dogs (age range 5-8 years) of both sexes can be affected. Unfortunately there is not a completely effective treatment, however many are improved on anti-epileptic drugs.

Although the myoclonus (jerking) and epilepsy can get worse it does not appear to shorten the life of affected dogs; they do not appear to develop the severe neurological signs (dementia, status epilepticus, death) that characterises the human form of the disease, which occurs because affected dogs are missing a vital enzyme involved with carbohydrate metabolism. This results in the storage of a polyglucasan storage material (Lafora bodies) within the brain and some other tissues. The material interferes with synaptic transmission. Diagnosis is by identification of the Lafora bodies in a liver, muscle or nerve biopsy.

At present we are searching for the abnormal gene which causes this disease. If the gene can be located then the disease could be diagnosed by a blood test. This is especially important as the disease develops after the breeding age. In an attempt to search for the gene we are collecting blood and pedigrees from affected dogs (and also blood from related and normal miniature wirehaired dachshunds) for DNA analysis.

For DNA analysis I would be grateful if you could obtain 10ml of blood in EDTA and label clearly with the dogs name and whether it is an affected, related or normal dog. The samples should be sent via FedEx (charge to account number 2106-2367-1, FedEx phone number is 0800 123 800). To Berge Minnasian, Dept of Genetics, The Hospital for Sick Children, 9107 Elm, 555 University Place, Toronto, M5 G1XA. It is very helpful if you can fax the hospital to warn them that a sample is on its way on 001 416 813 8319.

Please do not send samples on a Friday, as they tend to sit over the weekend.

Please send the case history and pedigrees of affected dogs to me.

Thank you for your help.

Clare Rusbridge BVMS DipECVN MRCVS