Abstract
Lafora's disease is a neurodegenerative disorder caused by recessive loss-of-function
mutations in the EPM2A (laforin glycogen phosphatase) or EPM2B (malin E3 ubiquitin ligase) genes. Neuropathology is characterized by malformed precipitated
glycogen aggregates termed Lafora bodies. Asymptomatic until adolescence, patients
undergo first insidious then rapid progressive myoclonus epilepsy toward a vegetative
state and death within a decade. Laforin and malin interact to regulate glycogen phosphorylation
and chain length pattern, the latter critical to glycogen's solubility. Significant
gaps remain in precise mechanistic understanding. However, demonstration that partial
reduction in brain glycogen synthesis near-completely prevents the disease in its
genetic animal models opens a direct present path to therapy.
Keywords
Lafora Disease - progressive myoclonus epilepsy - polyglucosan body
