Lafora's Disease
What it does to teenagers and what we're going to do with it
By Berge A. Minassian, MD, CM, FRCPC, and Stephen W. Schere, PhD, Hospital for Sick Children, Toronto, ON
Lafora's progressive myoclonus epilepsy is the most severe epilepsy syndrome. It begins in early adolescence. The first seizures are myoclonic (jerk-like) movements, visual hallucinations, or both. The hallucinations can be of bright lights or figures or much more complex visions, usually of frightful scenes and people. The jerks soon become impossible to deny or hide. They worsen with emotion and are embarrassing to the teenager who has to deal with them along with hallucinations. Within the first two years, generalized convulsions begin to occur. Meanwhile, mental abilities begin a gradual decline. All symptoms worsen over time, become intractable to any form of treatment, and lead to death within 10 years. In many cases, because Lafora's is an inherited condition, younger siblings, who have to witness this progressive decline, have a 25% chance of developing the disease themselves.
The disorder was described in 1911 by the Spanish pathologist Gonzalo Lafora, who worked in an asylum for the insane in the United States. In 1998, our team at The Hospital for Sick Children in Toronto, ON, identified the gene responsible for this disease. This work was carried out in collaboration with Dr. Guy Rouleau and Dr. Eva Andermann in Montreal and many other colleagues worldwide.
Our aim is to obtain a complete and detailed understanding of the pathophysiology of Lafora's disease. Our hope is that when or while we achieve this goal, we will have enough insights to intervene and prevent or cure the disease.
We've been thoroughly analyzing a protein product, encoded by the Lafora gene, which we have named laforin. Laforin seems to be involved with regulating the function of other proteins.We are in the midst of performing experiments to identify the proteins with which laforin interacts, and we have some exciting discoveries in this area, which will soon be published.
Laforin has a carbohydratebinding domain, with which it seems to bind to glycogen. This is an important piece of the puzzle, because abnormally formed glycogen deposits are found in the neurons of patients with the disease. These deposits are often so large that they outgrow and destroy the brain cells. When smaller, they occupy neuronal dendrites and likely cause severe seizures.
We have recently generated a mouse model of Lafora's disease. This model is allowing us to study the pathology of this disease and epilepsy in greater detail. Finally, we have come across a breed of purebred dogs which have this disorder. No experiments are planned on this natural model of Lafora's disease. However, DNA obtained from these dogs is allowing us to track down a second gene in humans, which causes the same condition.
Lafora's disease, thankfully, is rare. To the families afflicted by it, rare means nothing at all. In fact, it only means that few people will study the disease, delaying any hope for a cure. We are fortunate that the Canadian Institute for Health Research and The Hospital for Sick Children have seen the wisdom of supporting our work.
We believe that what we learn in this most severe of epilepsies will teach us a lot about the more common epilepsies. We cherish the thought that, some day, a neurologist will diagnose a child with Lafora's disease and, in the next breath, tell the parents, "Don't worry. It will be all right, and make sure you bring your younger children to see me."
Printed with permission of Epilepsy Canda.
