Broccolini Aldobrando, Gidaro Teresa, Morosetti Roberta, Mirabella Massimiliano
Department of Neuroscience, Catholic University, L.go A. Gemelli 8, 00168 Rome, Italy.
Muscle Nerve. 2009 Sep;40(3):340-9. doi: 10.1002/mus.21385.
Hereditary inclusion-body myopathy (h-IBM), or distal myopathy with rimmed vacuoles (DMRV), is an autosomal recessive disorder with onset in early adult life and a progressive course leading to severe disability. h-IBM/DMRV is due to mutations of a gene (GNE) that codes for a rate-limiting enzyme in the sialic acid biosynthetic pathway. Despite the identification of the causative gene defect, it has not been unambiguously clarified how GNE gene mutations impair muscle metabolism. Although numerous studies have indicated a key role of hyposialylation of glycoproteins in h-IBM/DMRV pathogenesis, others have demonstrated new and unpredicted functions of the GNE gene, outside the sialic acid biosynthetic pathway, that may also be relevant. This review illustrates the clinical and pathologic characteristics of h-IBM/DMRV and the main clues available to date concerning the possible pathogenic mechanisms and therapeutic perspectives of this disorder.
遗传性包涵体肌病（h-IBM），或伴有镶边空泡的远端肌病（DMRV），是一种常染色体隐性疾病，发病于成年早期，病程呈进行性发展，最终导致严重残疾。h-IBM/DMRV是由一个基因（GNE）的突变引起的，该基因编码唾液酸生物合成途径中的一种限速酶。尽管已经确定了致病基因缺陷，但GNE基因突变如何损害肌肉代谢尚未得到明确阐明。虽然众多研究表明糖蛋白低唾液酸化在h-IBM/DMRV发病机制中起关键作用，但其他研究也证明了GNE基因在唾液酸生物合成途径之外的新的、未预测到的功能，这些功能可能也与之相关。本综述阐述了h-IBM/DMRV的临床和病理特征，以及迄今为止关于该疾病可能的致病机制和治疗前景的主要线索。
