Progressive myoclonus epilepsy of Lafora

Excerpt

Lafora disease is an autosomal recessive form of progressive myoclonus epilepsy characterized by a severe course that leads to death in 5–10 years in most patients. Patients present myoclonic, absence and generalized tonic-clonic seizures at onset, tipically at around age 14–15 years. As the disease progresses, difficulties in speech generation and gait as well as cognitive decline appear. Seizures soon become intractable and due to a rapidly progressing dementia patients become severely incapacitated and die. Lafora bodies are the characteristic hallmark and consist of an abnormal, poorly branched, intracellular glucose polymer accumulating in many tissues including heart, skeletal muscle, liver, and brain. They can be observed on optic microscopy as periodic acid-Schiff-positive (PAS+) cytoplasmic inclusions. Lafora bodies thus resemble glycogen with reduced branching, suggesting an alteration in glycogen metabolism as the cause of their accumulation. Since the discovery of the localization of the first gene for Lafora disease in 1995, major advances have led to a better understanding of the basic mechanisms involved in this adolescent-onset and deadly disease.