Lafora disease is also known as progressive myoclonic elepsy 2 or Lafora inclusion body disease. It is an inherited neurologic disorder that belongs to the group of polyglucosan diseases and progressive myclonic epilepsies. It is characterized by muscle spasms, hallucinations, dementia, and complete loss of cognitive abilities. This lethal neurodegenerative disease has an insidious onset in childhood or adolescence.
What is Lafora disease?
Lafora disease is an autosomal recessive disorder characterized by involuntary, violent, and generalized muscle twitching. The first symptoms and complaints appear in young people during childhood or adolescence. This neurological disease has no cure to date and is regularly lethal. Those affected rarely live beyond the age of 25. They suffer from hallucinations, and as the disease progresses, dementia and loss of cognitive abilities also set in. The prevalence in the Western world is one in a million and increases in geographically isolated areas and regions where intermarriage among relatives is not uncommon.
Causes
The cause is an autosomal recessive inherited gene mutation of the genes EPM2A, encoding the enzyme laforin, and NHLRC1, encoding malin, which contains amino acids and zinc. This is a rare fatal form of epilepsy that is passed from both parents to the child through recessive inheritance. Although the parents themselves carry the genetic defect responsible for this disorder, it is not expressed in them. In rare cases, Lafora disease is not inherited recessively, but is the result of a random gene mutation. There are several control systems in the brain that prevent the accumulation of excessive amounts of sugar in the nerve cells. Sentinel proteins ensure that these control systems function smoothly. For most of the body’s cells, sugar in its storage form glycogen is a welcome energy supplier. For brain cells, however, it is lethal. In healthy people, the carbohydrate store remains turned off so that it is not inadvertently activated. In people suffering from Lafora disease, this control mechanism is suspended and small sugar clumps in the form of glycogen dock onto the brain cells and switch them off. The two proteins of the responsible genes prevent glycogen production. They are so closely linked that the defect in one protein also disables the second gene involved. The control mechanism is disrupted and triggers different reactions that favor the storage of glycogen granules on brain cells, ultimately leading to neuronal death.
Symptoms, complaints, and signs
The consequences of this glycogen accumulation in the brain cells have devastating effects on the organism. Affected individuals suffer from epileptic seizures characterized by violent and voluntary muscle spasms and twitching. The patient has difficulty coordinating his movements and muscle functions. In addition, hallucinations, memory lapses and thinking difficulties set in, leading to dementia as the disease progresses. In the final stage, a significant decline in cognitive performance with temporary blindness sets in. The epileptic seizures become more frequent and more
more violent.
Diagnosis and course of the disease
As the disease progresses, the symptoms and complaints worsen, since no successful therapy for this neurodegenerative hereditary disease exists yet. For this reason, it is always lethal, with patients usually dying within ten years of diagnosis. In the final stage of the disease, the patient’s cognitive abilities and physical condition are so limited that he or she becomes a nursing case. Hospitalization may also be necessary. The treating physician performs a skin biopsy, or alternatively a liver or brain biopsy, to obtain final certainty as to whether the patient is indeed suffering from Lafora disease. The biopsy is supported by various genetic tests. In addition to the patient, the patient’s parents are also tested to determine if they are carriers of this genetic defect.This hereditary genetic testing provides the treating physician with the final certainty that it is an autosomal recessive inheritance and not a random gene mutation.
Complications
Lafora disease is associated with very serious symptoms and signs. It can also lead to the death of the patient in the worst case if treatment of this disease is not initiated. As a rule, patients with this disease suffer from muscle spasms and furthermore from epileptic seizures. The quality of life of the affected person is considerably reduced by these complaints. It is also not uncommon for pain to occur. The patients show involuntary movements and can no longer control their muscles independently. In many cases, they are therefore dependent on the help of other people in their daily lives. Likewise, memory lapses may also occur. Those affected also suffer from thinking difficulties and symptoms of dementia. Especially for relatives or for parents, Lafora disease can cause severe psychological discomfort or depression. Furthermore, the disease can also lead to blindness. It is not possible to treat Lafora disease causally. For this reason, treatment is symptomatic and depends on the symptoms. However, a completely positive course of the disease does not occur, so that in most cases patients are dependent on the help and support of other people throughout their lives.
When should one go to the doctor?
Parents who notice signs of Lafora disease in their child should talk to their pediatrician immediately. The disease progresses rapidly and has not yet been treatable causally, so symptomatic therapy must be initiated early. Characteristic symptoms such as seizures, hallucinations or learning disorders require rapid clarification. Should further symptoms develop, medical advice is required in any case. The physician can perform a biopsy and rule out or diagnose the disease. If Lafora disease is indeed present, therapeutic measures must be started promptly. During therapy, a physician must be consulted at regular intervals. If the prescribed medication causes side effects or has no effect, the responsible medical professional must be informed. Since Lafora disease is a hereditary disease, a diagnosis in the womb is possible if there is a concrete suspicion. Therefore, if one of the parents suffers from the disease, a genetic examination should take place. This will allow treatment to begin immediately after birth.
Treatment and therapy
This neurodegenerative disease has no cure to date, and the symptoms and complaints worsen within a comparatively short period of time, so that patients usually do not live past 25 years of age. The treating physician can only prescribe anticonvulsant drugs to reduce the muscle contractions and thus the patient’s suffering. Preferably, the treating physician prescribes a muscle relaxant (myotonolytic) such as clonazepam and antiepileptic drugs such as valproic acid. Clonazepam, a member of the benzodiazepine group, is already used in children suffering from epilepsy. It has a spasm-suppressing effect and relaxes the muscles. Valproic acid is an effective form of therapy for generalized forms of epilepsy, which also has an impulse- and mood-stabilizing effect. These two drugs can only positively accompany the course of Lafora’s disease and reduce the symptoms, but not cure it or enable the patient to lead a normal life in the long term, depending on the circumstances. In addition to drug therapy, psychological support for the patient and parents is also recommended.
Outlook and prognosis
Lafora disease has been little studied. It occurs in about one in a million people. Scientists believe it is inherited and transmitted through childbearing among relatives. There are no prospects for a cure. Doctors try to stop acute symptoms. Life expectancy is significantly minimized. Almost all affected persons do not even reach the age of 25. The onset of typical symptoms is in the second decade of life. Patients then have four to ten years left in which cognitive abilities decline and convulsions steadily increase.It is not advisable to forgo treatment. Although the life time remains the same, doctors can alleviate many complaints. Thus, the pain of deterioration can be contained. The disease is stressful not only for the patient but also for family members. Psychotherapies can explore meaningful questions and address or structure the journey toward the end of life. The prognosis after a diagnosis of Lafora disease could not be more unfavorable. Sufferers are in need of help during their short lives. The development of a professional perspective is narrowly limited from the outset.
Prevention
Most affected individuals are unaware that they suffer from this disorder until a final diagnosis is made. Because it is a rare gene mutation that is transmitted to the child by both parents, prevention in the clinical sense is not possible. As a rule, it is only with the final diagnosis and further genetic testing that parents learn that they too are carriers of this genetic defect, which, however, has not broken out in themselves.
Follow-up
In most cases of Lafora disease, the measures of aftercare are severely limited, so those affected by this disease are in any case dependent on intensive medical treatment. First and foremost, this is designed to prevent further deterioration of the symptoms. Self-cure cannot occur with Lafora disease, so that treatment by a doctor must always take place. In most cases, various medications must be taken to alleviate the symptoms of this disease. However, a complete cure cannot be achieved, so that most of those affected die at a very young age. The life expectancy of the affected person is therefore significantly reduced by Lafora disease. Due to the symptoms, most of those affected are dependent on the help and also the support of friends and family in their lives. In this context, loving and intensive conversations also have a positive effect on the psychological state of the affected person and can prevent further psychological upsets or even depression. In the case of a desire to have children, Lafora disease should always be followed by genetic testing and counseling to prevent the recurrence of the disease.
What you can do yourself
Lafora disease is a serious condition that is fatal in the worst cases. For this reason, therapeutic counseling is recommended first and foremost for those affected and their relatives. Since the disease is usually diagnosed in childhood, early counseling makes sense. Together with the psychologist, a decision can then be made about the next steps. In most cases, the affected child must attend a special kindergarten and later a special school – both should be initiated as early as possible to avoid problems later on. Medical care is also required for Lafora disease. The sufferer must be examined regularly in the doctor’s office so that any complications can be dealt with quickly and in a targeted manner. Various medications can be prescribed for the typical muscle spasms and uncoordinated movements. Parents should always make sure to keep an eye on the child and intervene immediately in case of cramps. If the child is directly calmed and immobilized, at least accidents and falls can be avoided. In addition, the risk of panic attacks is reduced if a trusted person is nearby to reassure the sufferer.
