ABSTRACT

Lafora Disease (LD) is a fatal neurodegenerative condition characterized by the accumulation of abnormal glycogen inclusions known as Lafora bodies (LBs). Patients with LD manifest myoclonus and tonic-clonic seizures, visual hallucinations, and progressive neurological deterioration beginning at the age of 8-18 years. Mutations in either EPM2A gene encoding protein phosphatase laforin or NHLRC1 gene encoding ubiquitin-ligase malin cause LD. Approximately, 200 distinct mutations accounting for the disease are listed in the Lafora progressive myoclonus epilepsy mutation and polymorphism database. In this review, the genotype-phenotype correlations, the genetic diagnosis of LD, the downregulation of glycogen metabolism as the main cause of LD pathogenesis and the regulation of glycogen synthesis as a key target for the treatment of LD are discussed.

Keywords: EPM2A ve NHLRC1 gen mutasyonlar, genotip-fenotip ilişkisi, Lafora progresif miyoklonus epilepsi, LD patojenezi