Malicdan May Christine V, Noguchi Satoru, Nishino Ichizo
National Institute of Neurosciences, National Center of Neurology and Psychiatry, Tokyo, Japan.
Curr Opin Neurol. 2008 Oct;21(5):596-600. doi: 10.1097/WCO.0b013e32830dd595.
Distal myopathy with rimmed vacuoles or hereditary inclusion body myopathy is an adult-onset autosomal recessive, slowly progressive and debilitating myopathy due to mutations in the gene that regulates the synthesis of sialic acid. This review aims to update our knowledge of this myopathy and to review studies about pathomechanism and therapeutic strategies.
Owing to the mutated gene, it was expected that the pathomechanism of this myopathy would be based on hyposialylation, a highly controversial phenomenon. This concept has been supported by findings in two recently generated animal models. In addition, the intracellular amyloid-beta accumulation in a distal myopathy with rimmed vacuole mouse model is relevant to similar findings in patients.
Clarifying the role of hyposialylation in distal myopathy with rimmed vacuole/hereditary inclusion body myopathy could potentially lead to a therapeutic strategy for this progressive myopathy. In addition, strategies aimed at preventing amyloid-beta deposition or enhancing its clearance could also be beneficial, as this epiphenomenon is now known to occur early in the course of the disease.
伴有镶边空泡的远端肌病或遗传性包涵体肌病是一种成人发病的常染色体隐性、缓慢进展且使人衰弱的肌病，由调控唾液酸合成的基因突变所致。本综述旨在更新我们对这种肌病的认识，并回顾有关发病机制和治疗策略的研究。
由于该基因突变，预计这种肌病的发病机制将基于唾液酸低糖化，这是一个极具争议的现象。这一概念已得到两个最近构建的动物模型研究结果的支持。此外，在伴有镶边空泡的远端肌病小鼠模型中细胞内β淀粉样蛋白的积累与患者的类似发现相关。
阐明唾液酸低糖化在伴有镶边空泡的远端肌病/遗传性包涵体肌病中的作用可能会为这种进行性肌病带来治疗策略。此外，旨在预防β淀粉样蛋白沉积或增强其清除的策略也可能有益，因为现在已知这种附带现象在疾病进程早期就会出现。
