Lafora's disease

Lafora disease is a fatal autosomal recessive, genetic disorder characterized by the presence of inclusion bodies, known as Lafora bodies, within the cytoplasm of the cells in the heart, liver, muscle, and skin.:545 Lafora disease is also a neurodegenerative disease that causes impairment in the development of cerebral cortical neurons and is a glycogen metabolism disorder. Lafora disease is a fatal autosomal recessive, genetic disorder characterized by the presence of inclusion bodies, known as Lafora bodies, within the cytoplasm of the cells in the heart, liver, muscle, and skin.:545 Lafora disease is also a neurodegenerative disease that causes impairment in the development of cerebral cortical neurons and is a glycogen metabolism disorder. Dogs can also have the condition. Typically Lafora is rare in American children but has a high incidence in children of Southern European descent (Italy, France, Spain) and can also be found in children from South Asian countries (Pakistan, India) and even as far south as North Africa. In canines, Lafora disease can spontaneously occur in any breed, but the Miniature Wire Haired Dachshund, Bassett Hound, and the Beagle are predisposed to LD. Most patients with this disease do not live past the age of twenty-five, and death within ten years of symptoms is usually inevitable. At present, there is no cure for this disease but there are ways to deal with symptoms through treatments and medications. Symptoms of Lafora disease begin to develop during the early adolescent years, and symptoms progress as time passes. In the first ten years of life there is generally no indication of the presence of the disease. The most common feature of Lafora disease is seizures that have been reported mainly as occipital seizures and myoclonic seizures with some cases of generalized tonic-clonic seizures, atypical absence seizures, and atonic and complex partial seizures. Other symptoms common with the seizures are drop attacks, ataxia, temporary blindness, visual hallucinations, and a quickly-developing and dramatic dementia. Other common signs and symptoms associated with Lafora disease are behavioral changes due to the frequency of seizures. Over time those affected with Lafora disease have brain changes that cause confusion, speech difficulties, depression, decline in intellectual function, impaired judgement and impaired memory. If areas of the cerebellum are affected by seizures, it is common to see problems with speech, coordination, and balance in Lafora patients. For dogs that are affected with Lafora disease, common symptoms are rapid shuddering, shaking, or jerking of the canine's head backwards, high pitched vocalizations that could indicate the dog is panicking, seizures, and as the disease progresses dementia, blindness, and loss of balance. Lafora disease is an autosomal recessive disorder, caused by loss of function mutations in either laforin glycogen phosphatase gene (EPM2A) or malin E3 ubiquitin ligase gene (NHLRC1). These mutations in either of these two genes lead to polyglucosan formation or lafora body formation in the cytoplasm of heart, liver, muscle, and skin. EPM2A codes for the protein laforin, a dual-specificity phosphatase that acts on carbohydrates by taking phosphates off. NHLRC1 encodes the protein malin, an E3 ubiquitin ligase, that regulates the amount of laforin.