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A BRIEF OVERVIEW OF LAFORA DISEASE
Lafora Disease is an inherited myoclonus epilepsy syndrome. Most cases of Lafora disease are caused by mutations in one of two known genes: EMP2A and EMP2B. Both genes are located in chromosome 6. The gene EPM2A makes the protein called Laforin and the gene EPM2B makes the protein called Malin. A few cases of Lafora disease are caused by an as yet unidentified gene(s). Lafora disease causes seizures, muscle spasms, difficulty walking, dementia, and eventually death.
The disease most commonly starts as epileptic seizures in adolescence. Rarely, it begins in 5 to 6 year old children as a learning disorder. There is a higher incidence of the disease in children of Middle Eastern, Southern European (Spain, France and Italy), South Asian (India and Pakistan) and North African descent. The disease appears to affect males and females equally.
There is currently no therapy that has proven effective against disease progression. Therapy is primarily palliative and aimed at reducing seizures.
We are raising funds for two forms of treatment on the horizon, one on the immediate horizon is gentamycin treatment and the other on the near horizon is called gene replacement treatment using pegylated immunoliposomes (PIL). Note: Any trials that are considered “research” will first require review and approval by an Institutional Review Board (Human Subjects Protection Committee) and this can take considerable time and coordination by someone on the team.
Lafora Disease currently receives very little, if any, funding from the Federal Government; perhaps because the disease is extremely rare in the United States. It is currently unknown how many children in the United States suffer from Lafora Disease. Although it is a rare, “orphan” disease, we are determined to find a cure for Chelsea’s hope and the hope of other children with Lafora Disease in other parts of the world.
Symptoms
Lafora Disease symptoms usually appear in the late stages of childhood and early adolescence. In most cases, patients develop normally for roughly the first ten years of their life. The first symptom to usually manifest is called a tonic-clonic seizure, a seizure that affects the entire body. Tonic-clonic grand mal seizures are characterized by extreme muscle tension and rapid muscle contractions. In other cases, the first symptom may be a seizure, induced by flickering light, characterized by staring for 1-10 seconds (absences or petit mal seizures) with momentary loss of responsiveness and a disconnection with the surrounding environment. Eventually, all develop the characteristic lightning-like muscular jerks that shake the shoulders, arms, legs or body and face. Such quick myoclonic spasms can affect a fragment of muscles in arms and shoulders on one side or both sides of the body and are triggered by touch, light or sound, appear almost continuously and are the reason for calling Lafora Disease a myoclonic epilepsy. Other symptoms include temporary blindness, visual hallucinations, depression, diminishing performance in school, ataxia (difficulty walking), and dementia.
In general, the following are symptoms that may indicate possible Lafora disease. If your child begins to demonstrate the combination of the following symtoms, immediately speak with your child's doctor about Lafora Disease and about having a skin biopsy and mutation analyses.
- Tonic-clonic seizures (full body seizures)
- Flickering-light induced absence and myoclonic seizures
- Reports of temporary blindness
- Visual hallucinations
- Depression
- Unexplained diminishing academic performance
- Difficulty walking (ataxia)
- Problems in thinking (Dementia)
Both skin biopsy and mutation analyses are necessary to prove lafora disease.
Why Skin Biopsy:
Biopsy of sweat glands in the axilla (arm pit) should show the disease causing inclusion bodies that stain with PAS (periodic acid schiff) inside eccrine sweat duct cells or apocrine myoepithelial cells located in the arm pits. These inclusion bodies are made of abnormally branched glycogen called polyglucosan and was originally discovered by Gonzalo Lafora in the patients’ brains. This separates Lafora Disease from other progressive myoclonic epilepsies. The presence of PAS+ inclusion bodies means you (your child) have Lafora Disease. If the skin biopsy is negative but you (your child) still have the above symptoms of Lafora Disease, it is reasonable to get a muscle or liver biopsy.
Why Mutation Analyses:
There are two reasons for mutation analyses.
First, PAS+ inclusion bodies may be present in your skin biopsy but mutations in EPM2A or EPM2B are absent. This means you have the rare form caused by an as yet unidentified gene.
Secondly, it is now important to find out if the forms of mutations present are nonsense mutations. Nonsense mutations may respond to gentamycin treatment.
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