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 canines head backwards, high pitched vocalizations that could indicate the dog is panicking, seizures, and as the disease progresses dementia, blindness, and loss of balance.Within ten years of developing symptoms, life expectancy has known to go down. People who advance to adulthood tend to lose their ability to do daily tasks by themselves, which can lead them to having to have comprehensive care. If their symptoms have become onset extremely fast or at an early age, comprehensive care allows one to get treatment in ways that are not only regarding receiving their medication, but it also includes both physical and mental health towards the daily activities that one would normally perform by themselves. Genetics
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.Graph 1 shows the data for 250 families that have been affected by Lafora Disease and the distribution of cases around the world. The graph shows that there is a very large number of cases in Italy because of the EPM2A gene mutation compared to any other country in the world.
Graph 2 shows the percentage distribution of the cases from either an EPM2A gene mutation or an EPM2B (NHLRC1) gene mutation. 42% of the cases are caused by EPM2A and 58% are caused by EPM2B (NHLRC1). The most common mutation on the EPM2A gene is the R241X mutation. This genetic mutation is the cause for 17% of the EPM2A caused Lafora Disease cases.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.Laforin is essential for making the normal structure of a glycogen molecule. When the mutation occurs on the EPM2A gene, laforin protein is down-regulated and less amount of this protein is present or none is made at all. If there is also a mutation in the NHLRC1 gene that makes the protein malin, then laforin cannot be regulated and thus less of it is made. Less Laforin means more phosphorylation of glycogen, causing conformational changes, rendering it insoluble, leading to an accumulation of misformed glycogen, which has neurotoxic effects.