Lafora body disease: Description, Causes and Risk Factors:
A form of progressive myoclonus epilepsy (PME) beginning from age 6-19; characterized by generalized tonic-clonic
seizures, resting and action myoclonus, ataxia, dementia, and classic electroencephalography (EEG) findings, including polyspike and wave discharges; basophilic cytoplasmic inclusion bodies present in portions of the brain, the liver, and skin, as well as the duct cells of the sweat glands. Death usually occurs within 10 years of onset; autosomal recessive inheritance, caused by mutation in the progressive myoclonic epilepsy 2 gene (EPM2A) on chromosome 6q.
The etiology of Lafora body disease is unknown and it affects both sexes equally. Although polyglucosans inclusions are characteristic of this disease, as of yet no enzymatic deficiency or abnormality in carbohydrate metabolism has been demonstrated.
Lafora body disease is thought to be caused by a defect in carbohydrate metabolism. Pathognomonic Lafora bodies are intracellular bodies formed of abnormal glycogen named polyglucosan. These bodies are deposited in neurons and other tissues including the heart, liver, muscle and skin. Lafora disease is inherited in an autosomal recessive manner. Mutations in EPM2A gene located in the region of 6q23-25 and EPM2B gene located in the region of 6p22-32 are responsible for the disease. EPM2A gene encodes tyrosine phosphatase (Laforin protein) and EPM2B gene encodes malin protein; both proteins remove polysaccharides from the cell by tyrosine phosphatase activity.
In most of the cases, generalized seizures are the first symptoms of the disease. Mental decline starts usually later in the course of the disease, but it can rarely also be the initial finding. Researchers reported that epileptic seizures can be responsible for personality deterioration and mental decline. Visual ictal phenomena appear in half of the cases and are a relatively specific clinical clue to the diagnosis of disease, but this clinic feature was absent in our case. The characteristic EEG pattern consists of slow background recurrent epileptiform discharges including spikes, polyspikes, spike-wave and polyspike-wave complexes. Additionally, it has been shown that EEG remains almost unchanged with disease progression.
These disorders tend to get worse over time. Lafora body disease is one of at least three of the recognized types of PME and is characterized by the presence of carbohydrate particles known as Lafora bodies in the cells of the nervous system, muscles and/or skin.
Patients develop the first symptoms mainly during adolescence. Major problems include seizures
, drop attacks, myoclonus
, ataxia, and, most significantly, a quickly developing, progressive and severe dementia.
Demonstration of Lafora bodies by biopsy is diagnostic. Since Lafora bodies are observed in the eccrine and apocrine ducti, the axilla is the most appropriate region for biopsy. Cutaneous biopsy should involve eccrine and apocrine sweat glands. False negative results are frequently found because of sampling errors. Genetic diagnosis is possible. In all cases, both genes have been found to be mutated.
The diagnosis may be confirmed by the demonstrationof typical spherical PAS-positive inclusion bodies in thebrain and spinal cord, heart and liver, skeletal muscle andaxillary sweat gland duct cells. Thoseinclusions are polyglucosan bodies which are not specificfor Lafora body disease. Similar changes can also be seen in certainconditions and diseases such as normal aging, type IVglycogen storage disease, arylsulfatase Apseudodeficiency, some instances of amyotrophic lateralsclerosis and upper or lower motor neuron disease.Myoclonus bodies are often seen in neuropil and neuronalperikarya in LB, but locate in axons and astrocytes inadult polyglucosan disease. Corpora amylaceawhich is a normal feature of the aging brain, imitatesLafora bodies, but it is not found in neuronal structures.
Treatment for Lafora body disease focuses on medication that provides symptomatic relief and support in the care of the individual. Clonazepam is sometimes used to treat the myoclonus. Sometimes a combination of medications is required in order to control some of the symptoms.
NOTE: The above information is educational purpose. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition.
DISCLAIMER: This information should not substitute for seeking responsible, professional medical care.