Rare Disease: Lafora Disease

rare-diseases-hub-300x250Our physicians regularly discuss Rare Diseases, as they consult on patient cases and keep up with the latest medical research, especially through our partnership with Global Genes.  Dr Linda Girgis started a discussion about Laforna disease in the community.  If you are a physician, please join us.

Lafora disease was first identified by the Spanish neurologist, Gonzalo Rodriguez Lafora , in 1911. This disease is a fatal autosomal recessive disorder, also known as Lafora progressive myoclonic epilepsy or MELF. It is characterized by inclusion bodies (also known as Lafora bodies)  in the cytoplasma of cells in the heart , liver,  muscle and skin. It is now considered to be a neurodegenerative disease, since there is impairment in the neurons of the cerebral cortec. Additionally, it is considered a glycogen metabolism disorder, because of these Lafora bodies. These bodies are made up of abnormal glycogen called polyglucosans. 1

Typically, patients with Lafora Disease experience recurrent seizures and intellectual decline.  It usually first appears in late childhood or adolescence and is marked by a rapid decline.  Early symptoms may include behavioral changes, depression, confusion and speech difficulties.  Seizures can be myoclonic, grand-mal or occipital and are difficult to treat. As the disease progresses, dementia sets in.  Additionally, the associate seizures worsen and become more difficult to treat.  Affected people usually lose their ability to perform ADLS within their 20s and usually die within 10 years of when the symptoms first appear. 2 Lafora disease has been seen world-wide but in western countries, the incidence is estimated to be less than 1 in one million. 3

The genetics of Lafora Disease have been fairly well studied. In 20012, Ganesh etal.  Found mutations EPM2A gene. In fact they discovered 2 genetic sub-types.  In classic Lafora Disease characterized  by “adolescent-onset stimulus-sensitive grand mal, absence, and myoclonic seizures followed by dementia and neurologic deterioration”, they found the mutation in exon 4.  In atyptical Lafora Disease, which is characterized by childhood onset, dyslexia and learning disorder followed by seizures and neurologic deterioration, they found the mutations mainly on exon 1.  They further studied the 5 missense mutations in the carbohydrate-binding domain and the 3 missense mutations in the dual phosphatase domain. 4

Mutations in the NHLRC1 gene have also been detected.  These genes, along with the EPM2A gene, encode the proteins that are important in the survival in the nerve cells in the brain.  Mutations interfere with the formation of functional proteins leading to the formation of Lafora bodies. These bodies are essentially clumps of abnormal glycogen that cannot be broken down and used for fuel within cells.  A build-up of these bodies is especially damaging to the cells in the nervous system. 5

Usually the diagnosis is made when suggestive signs and symptoms are present.  Often a skin biopsy can be done to detect the presence of Lafora bodies.  This biopsy is most commonly done in the axilla and looking for Lafora bodies in the sweat gland cells. Most people with this disorder will have these inclusion bodies on the biopsy results.  Genetic testing can also be done looking for mutations on the EPM2A gene or NHLRC1 gene. MRI and EEG are also helpful to exclude other diagnoses in the differential diagnosis. 6


Unfortunately, there is no current treatment available for Lafora Disease. There is similarly no way to slow its progression.  Medications should be used to treat the seizures and later in the disease, a feeding tube may be needed.  7



Dr. Linda Girgis MD, FAAFPdr linda headshot is a family physician in South River, New Jersey. She has been in private practice since 2001. She holds board certification from the American Board of Family Medicine and is affiliated with St. Peter’s University Hospital and Raritan Bay Hospital. She teaches medical students and residents from Drexel University and other institutions.  Dr. Girgis earned her medical degree from St. George’s University School of Medicine. She completed her internship and residency at Sacred Heart Hospital, through Temple University where she was recognized as intern of the year.  She is a blogger for Physician’s Weekly and MedicalPractice Insider as well as a guest columnist for Medcity News and HIT Outcomes. She has had articles published in several other media outlets. She has authored the books, “Inside Our Broken Healthcare System” and “The War on Doctors”.  She has been interviewed in US News and on NBC Nightly News.

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