Lafora disease is a rare genetic disorder involving glycogen metabolism disorder. It is inherited by autosomal recessive pattern presenting as a progressive myoclonus epilepsy and neurologic deterioration beginning in adolescence. It is characterized by Lafora bodies in tissues such as brain, skin, muscle, and liver.
Signs and Symptoms
- Onset of symptoms between 8-19 years, peak at 14-16 years; rare early onset in children as young as 5 years
- Initial symptoms: headaches, learning difficulties, and seizures
- Most common seizures: myoclonic seizures (jerking or shaking movements)
- Other seizure types:
- Tonic-clonic (muscle stiffening followed by jerking)
- Absence (staring spells)
- Atonic (body becomes limp)
- Complex partial (staring spells with jerking or repetitive movements)
- Focal occipital (blindness or hallucinations)
Causes
- Caused by mutations in EPM2A or EPM2B (NHLRC1) genes
- EPM2A encodes laforin, EPM2B encodes malin; the malin-laforin complex regulates glycogen elongation
- Uncontrolled elongation leads to "Lafora bodies," abnormal glycogen particles damaging cells
- Lafora bodies accumulate in the nervous system, muscle, liver, and skin, causing symptoms
- Inheritance: Autosomal recessive pattern
- Both parents must carry the mutated gene for a 25% chance of an affected child per pregnancy
Affected Populations
- Equally affects adolescent males and females
- Higher frequencies in populations from the Mediterranean, Northern Africa, India, and Pakistan
- Estimated prevalence: 4 per 1,000,000 people (may be underestimated)
Disorders with Similar Symptoms
-
Juvenile Myoclonic Epilepsy (JME)
- Similar seizures but no progression, cognitive or motor deterioration
- Genetic cause rarely identified
Diagnosis