Lafora disease

Lafora disease is a rare, inherited, severe form of progressive myoclonus epilepsy [3]. It is characterized by an onset of symptoms between 8-19 years of age, with the peak symptom onset being between 14-16 years [1]. The condition most commonly begins with epileptic seizures in late childhood or adolescence [3].

Symptoms of Lafora disease may include:

• Frequent jerking movements (myoclonus) [2]
• Difficulty walking and muscle spasms [3]
• Dementia and rapid cognitive decline [8]
• Intractable seizures, difficulty walking, muscle spasms, neurological deterioration, rapid cognitive decline, dementia, and death [8]

Lafora disease is caused by loss-of-function mutations in either the EPM2A or EPM2B genes encoding laforin or malin, respectively [14]. The condition is autosomal recessive, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the disease [4].

Lafora disease is a severe and fatal neurodegenerative disorder, with death commonly occurring within 10 years of symptom onset [5]. It is characterized by the accumulation of glycogen-like inclusions in the cytoplasm of cells from most tissues of affected patients [15].

Overall, Lafora disease is a rare and devastating condition that affects individuals in late childhood or adolescence, leading to severe seizures, cognitive decline, and ultimately death.

Lafora Disease Signs and Symptoms

Lafora disease, also known as progressive myoclonus epilepsy, is a rare genetic disorder characterized by various signs and symptoms. The condition typically begins in late childhood or adolescence, with the peak symptom onset being between 14-16 years of age.

• Epileptic Seizures: Lafora disease often starts with epileptic seizures, which can be generalized tonic-clonic, atypical absence, or focal occipital seizures.
• Myoclonus: Myoclonus is a hallmark symptom of Lafora disease, characterized by sudden, involuntary muscle jerking or twitching that can affect part of the body or entire limbs.
• Difficulty Walking (Ataxia): Affected individuals may experience difficulty walking due to muscle spasms and coordination challenges.
• Dementia: As the disease progresses, patients often develop dementia, which is a gradual decline in cognitive function, including memory loss, confusion, and difficulty learning new information.
• Behavioral Changes: Behavioral changes, such as depression, apathy, and mood swings, are also common symptoms of Lafora disease.
• Speech Difficulties (Dysarthria): Some patients may experience speech difficulties due to muscle spasms or coordination challenges.
• Rapid Cognitive Decline: The condition is characterized by rapid cognitive decline, which can lead to significant impairments in daily life.

These symptoms can vary in severity and progression from person to person. Lafora disease is a severe form of progressive myoclonus epilepsy that typically ends in death 5-10 years after the initial symptoms.

References:

• [1] Signs & Symptoms. Lafora disease is characterized by an onset of symptoms between 8-19 years of age...
• [2] Lafora disease is an inherited, severe form of progressive myoclonus epilepsy.
• [3] Other signs and symptoms include difficulty walking, muscle spasms (myoclonus) and dementia.
• [4] Myoclonus is a term used to describe episodes of sudden, involuntary muscle jerking or twitching that can affect part of the body or entire limbs.
• [10] Symptoms of Lafora disease include: Seizures. Gradually increasing difficulty learning, thinking and processing information (cognitive decline). Difficulty speaking. Balance and coordination challenges. Stiff muscles . Behavioral changes. Mood changes (depression, apathy). Memory loss and dementia.
• [14] The signs and symptoms of Lafora disease most commonly begins with epileptic seizures in late childhood or adolescence. Other signs and symptoms include difficulty walking, muscle spasms (myoclonus) and dementia.

Lafora disease can be diagnosed through various tests, which are essential for an accurate diagnosis and treatment plan.

Diagnostic Tests:

• Skin Biopsy: A skin biopsy is a diagnostic test that involves taking a small sample of skin tissue from the patient's sweat ducts. This test can help detect Lafora bodies, which are characteristic of Lafora disease [2][4].
• Molecular Genetic Testing: Molecular genetic testing for pathogenic variants in the EPM2A or EPM2B genes confirms the diagnosis of

Current Drug Treatments for Lafora Disease

Lafora disease, a rare and lethal progressive myoclonus epilepsy, currently has no specific treatment. However, antiseizure medications are used to manage both seizures and myoclonus, with a low to moderate effect in some patients [4][5]. These medications include:

• Valproic acid
• Perampanel
• Benzodiazepines

Additionally, metformin has been designated an orphan drug for Lafora disease by the U.S. Food and Drug Administration (FDA) due to its potential benefits in treating the condition, particularly when started early in disease development [1][2]. However, it is not yet approved to treat Lafora disease.

Experimental Treatments

Researchers are exploring new treatment options, including:

• Gene therapy: delivering a functional copy of the defective gene to address the underlying cause of the disease [13]
• ASO genetic therapy: using antisense oligonucleotides (ASOs) to target and correct the genetic defect responsible for Lafora disease [12]

These experimental treatments hold promise, but more research is needed to determine their safety and effectiveness.

Other Medications

Phenobarbital, a wide-spectrum antiepileptic drug, may also be used in Lafora disease, with dosage ranges from 3 to 8 mg in children and 30 to 200 mg in adults [14].

It's essential to note that these treatments are not specific to Lafora disease and are primarily aimed at managing symptoms rather than addressing the underlying cause of the condition.

References:

[1] Context result 1 [2] Context result 2 [4] Context result 4 [5] Context result 5 [12] Context result 12 [13] Context result 13 [14] Context result 14

Differential Diagnosis of Lafora Disease

Lafora disease, also known as progressive myoclonus epilepsy (PME), is a rare genetic disorder characterized by the accumulation of inclusion bodies, known as Lafora bodies, within the cytoplasm of cells in various organs. The differential diagnosis of Lafora disease involves considering other conditions that may present with similar symptoms.

Conditions to Consider

• Unverricht-Lundborg Disease (ULD): This is another form of PME that affects young adolescents and presents with myoclonus, generalized tonic-clonic seizures, and progressive neurological deterioration. The age of onset is similar to Lafora disease, but the myoclonus is characteristically an action myoclonus, and tonic-clonic seizures are more easily controlled (13).