Lafora disease

Julie Turnbull, Erica Tiberia, Pasquale Striano, Pierre Genton, Stirling Carpenter, Cameron A. Ackerley, Berge A. Minassian

Research output: Contribution to journalReview article

26 Citations (Scopus)

Abstract

Lafora disease (LD) is an autosomal recessive progressive myoclonus epilepsy due to mutations in the EPM2A (laforin) and EPM2B (malin) genes, with no substantial genotype-phenotype differences between the two. Founder effects and recurrent mutations are common, and mostly isolated to specific ethnic groups and/or geographical locations. Pathologically, LD is characterized by distinctive polyglucosans, which are formations of abnormal glycogen. Polyglucosans, or Lafora bodies (LB) are typically found in the brain, periportal hepatocytes of the liver, skeletal and cardiac myocytes, and in the eccrine duct and apocrine myoepithelial cells of sweat glands. Mouse models of the disease and other naturally occurring animal models have similar pathology and phenotype. Hypotheses of LB formation remain controversial, with compelling evidence and caveats for each hypothesis. However, it is clear that the laforin and malin functions regulating glycogen structure are key. With the exception of a few missense mutations LD is clinically homogeneous, with onset in adolescence. Symptoms begin with seizures, and neurological decline follows soon after. The disease course is progressive and fatal, with death occurring within 10 years of onset. Antiepileptic drugs are mostly non-effective, with none having a major influence on the progression of cognitive and behavioral symptoms. Diagnosis and genetic counseling are important aspects of LD, and social support is essential in disease management. Future therapeutics for LD will revolve around the pathogenesics of the disease. Currently, efforts at identifying compounds or approaches to reduce brain glycogen synthesis appear to be highly promising.

Original languageEnglish (US)
Pages (from-to)S38-S62
JournalEpileptic Disorders
Volume18
DOIs
StatePublished - Jan 1 2016

Fingerprint

Lafora Disease
Glycogen
Progressive Myoclonic Epilepsy
Founder Effect
Phenotype
Sweat Glands
Behavioral Symptoms
Neurobehavioral Manifestations
Mutation
Skeletal Muscle Fibers
Genetic Counseling
Brain
Missense Mutation
Disease Management
Ethnic Groups
Cardiac Myocytes
Social Support
Anticonvulsants
Hepatocytes
Seizures

Keywords

  • EPM2A
  • EPM2B
  • glycogen phosphatase
  • Lafora
  • laforin
  • malin
  • progressive myoclonus epilepsies
  • ubiquitin

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Turnbull, J., Tiberia, E., Striano, P., Genton, P., Carpenter, S., Ackerley, C. A., & Minassian, B. A. (2016). Lafora disease. Epileptic Disorders, 18, S38-S62. https://doi.org/10.1684/epd.2016.0842

Lafora disease. / Turnbull, Julie; Tiberia, Erica; Striano, Pasquale; Genton, Pierre; Carpenter, Stirling; Ackerley, Cameron A.; Minassian, Berge A.

In: Epileptic Disorders, Vol. 18, 01.01.2016, p. S38-S62.

Research output: Contribution to journalReview article

Turnbull, J, Tiberia, E, Striano, P, Genton, P, Carpenter, S, Ackerley, CA & Minassian, BA 2016, 'Lafora disease', Epileptic Disorders, vol. 18, pp. S38-S62. https://doi.org/10.1684/epd.2016.0842
Turnbull J, Tiberia E, Striano P, Genton P, Carpenter S, Ackerley CA et al. Lafora disease. Epileptic Disorders. 2016 Jan 1;18:S38-S62. https://doi.org/10.1684/epd.2016.0842
Turnbull, Julie ; Tiberia, Erica ; Striano, Pasquale ; Genton, Pierre ; Carpenter, Stirling ; Ackerley, Cameron A. ; Minassian, Berge A. / Lafora disease. In: Epileptic Disorders. 2016 ; Vol. 18. pp. S38-S62.
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