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 of the heart, liver, muscle, and skin. In a later study, Lafora disease has been and is now viewed as a neurodegenerative disease, since prior to the actual formation of Lafora bodies there has been seen to be an impairment in the development of cerebral cortical neurons. It was further concluded that Lafora disease is a complex neurodegenerative disease and also a glycogen metabolism disorder
Patients develop the first symptoms mainly during adolescence. Major problems include seizures, drop attacks, myoclonus, ataxia, and, most significantly, a quickly-developing and severe dementia.
Lafora disease is an autosomal recessive disorder, caused by mutations in one of three known genes: EPM2A, EPM2B, and NHLRC1. EPM2A codes for the protein laforin, a dual-specificity phosphatase with a carbohydrate binding domain (CBM-20). Vertebrates have only one such protein with DSP domain as well as CBM-20 domain. EPM2B encodes the protein malin, an E3 ubiquitin ligase. All three discovered genes are present on chromosome 6p23-27 in humans.
Diagnosis is based on the clinical picture including history and EEG findings. The demonstration of Lafora bodies within the apocrine sweat gland of the skin by an axillary skin biopsy examination is a classic approach that may now be substituted by genetic testing. The inclusion bodies, which seem to contain high levels of carbohydrates, are typically labeled by a specific stain called PAS (Periodic acid-Schiff) which is resistant to diastase treatment. Under strong clinical suspicion, liver and brain biopsies may be undertaken. Currently the preferred method of certain diagnosis is DNA sequencing.
Lafora disease is distinguished by the presence of inclusions called "Lafora bodies" within the cytoplasm. Lafora bodies are composed of abnormal glycogen called polyglucosans. These starch-like polyglucosans are insoluble and hence precipitate inside cells.
Polyglucosan bodies appear with age; in Lafora disease, their numbers have increased enormously. Lafora bodies have been observed in virtually all organs of patients with the disease. In the brain, their presence appears to be restricted to neurons; they do not seem to present in astrocytes. Their morphology varies from tissue to tissue, but they generally contain a central core and have a peripheral fluffy appearance.
There is no treatment, and therapy is mainly supportive and symptomatic. Although seizure and myoclonus can be controlled for a long period by using antiepileptic drugs, patients rarely survive beyond one or two decades due to the devastating effects of dementia and ataxia. One medication, Zonisamide, has been shown to lengthen the life of those with the disease. This medication helps control and decrease the severity of the seizures affected patients often experience. Gene therapy strategies are being tried in a mouse model.