What causes Lafora disease?
Most cases of Lafora disease are caused by changes ( mutations ) in either the EPM2A gene or the NHLRC1 gene. These genes encode proteins that play a critical role in the survival of nerve cells (neurons) in the brain.
What disease is laforin involved in?
Laforin is a dual specificity protein phosphatase involved in Lafora disease (LD), a fatal form of progressive myoclonus epilepsy characterized by neurodegeneration and the presence of intracellular polyglucosan inclusions (Lafora bodies) in different tissues.
What is the disease laforin isoform involved in?
Lafora disease is the most severe teenage-onset progressive epilepsy, a unique form of glycogenosis with perikaryal accumulation of an abnormal form of glycogen, and a neurodegenerative disorder exhibiting an unusual generalized organellar disintegration.
What type of mutation is Laforin?
Laforin, encoded by the EPM2A gene, is a phosphatase, with a carbohydate-binding domain, which is mutated in patients with Lafora disease. It contains a dual specificity phosphatase domain (DSP) and a carbohydrate binding module subtype 20 (CBM20).
What is the function of laforin?
Laforin and malin likely play a critical role in regulating the production of a complex sugar called glycogen. Glycogen is a major source of stored energy in the body. The body stores this sugar in the liver and muscles, breaking it down when it is needed for fuel.
Who is Gonzalo Rodriguez Lafora disease named after?
The disease is named after Gonzalo Rodríguez Lafora (1886–1971), a Spanish neuropathologist who first recognized small inclusion bodies in Lafora patients. Since the discovery of Lafora Disease in early to mid 1900’s there has not been too much research into it, until more recent years.
What are the symptoms of Lafora disease LD?
With the exception of a few missense mutations LD is clinically homogeneous, with onset in adolescence. Symptoms begin with seizures, and neurological decline follows soon after. The disease course is progressive and fatal, with death occurring within 10 years of onset.
How is Lafora disease an autosomal recessive disease?
Lafora disease is inherited in an autosomal recessive manner. [2] This means that to be affected, a person must have a mutation in both copies of the responsible gene in each cell. The parents of an affected person usually each carry one mutated copy of the gene and are referred to as carriers.
What are the inclusions in Lafora disease called?
Lafora disease is distinguished by the presence of inclusions called “Lafora bodies” within the cytoplasm of cells. Lafora bodies are aggregates of polyglucosans or abnormally shaped glycogen molecules. Glycogen in Lafora disease patients has abnormal chain lengths, which causes them to be insoluble, accumulate, and have a neurotoxic effect.