Lafora disease (LD) is a teenage-onset fatal progressive myoclonus epilepsy caused by loss-of-function mutations in the EPM2A gene encoding the glycogen phosphatase laforin or EPM2B encoding the laforin-interacting ubiquitin E3 ligase malin. Concerted actions of glycogen synthase (GS) and branching enzyme generate normal short-branched soluble glycogen. In LD, some glycogen molecules develop long branches, precipitate, and accumulate into pathognomonic and pathogenic Lafora bodies (LBs). The precise mechanism by which the laforin-malin complex mitigates this is unknown, but thought to involve GS downregulation. In fact, transgenic GS downregulation in LD mouse models reduces LB formation and rescues the disease.^1,2

Lafora 病 (LD) 是一种青少年发作的致命性进行性肌阵挛性癫痫，由编码糖原磷酸酶 laforin的EPM2A基因或编码与laforin相互作用的泛素 E3 连接酶 malin 的 EPM2B 基因的功能丧失突变引起。糖原合酶 (GS) 和分支酶的协同作用产生正常的短支链可溶性糖原。在 LD 中，一些糖原分子长出分支、沉淀并积累成特征性和致病性的 Lafora 小体 (LB)。laforin-malin 复合物减轻这种情况的确切机制尚不清楚，但被认为涉及 GS 下调。事实上，LD 小鼠模型中的转基因 GS 下调减少了 LB 形成并挽救了疾病。^1,2