Medical Genetics Branch, National Human Genome Research Institute (NHGRI), National Institutes of Health, Bethesda, MD, 20892, USA.
Neurotherapeutics. 2018 Oct;15(4):900-914. doi: 10.1007/s13311-018-0671-y.
GNE myopathy, previously known as hereditary inclusion body myopathy (HIBM), or Nonaka myopathy, is a rare autosomal recessive muscle disease characterized by progressive skeletal muscle atrophy. It has an estimated prevalence of 1 to 9:1,000,000. GNE myopathy is caused by mutations in the GNE gene which encodes the rate-limiting enzyme of sialic acid biosynthesis. The pathophysiology of the disease is not entirely understood, but hyposialylation of muscle glycans is thought to play an essential role. The typical presentation is bilateral foot drop caused by weakness of the anterior tibialis muscles with onset in early adulthood. The disease slowly progresses over the next decades to involve skeletal muscles throughout the body, with relative sparing of the quadriceps until late stages of the disease. The diagnosis of GNE myopathy should be considered in young adults presenting with bilateral foot drop. Histopathologic findings on muscle biopsies include fiber size variation, atrophic fibers, lack of inflammation, and the characteristic "rimmed" vacuoles on modified Gomori trichome staining. The diagnosis is confirmed by the presence of pathogenic (mostly missense) mutations in both alleles of the GNE gene. Although there is no approved therapy for this disease, preclinical and clinical studies of several potential therapies are underway, including substrate replacement and gene therapy-based strategies. However, developing therapies for GNE myopathy is complicated by several factors, including the rare incidence of disease, limited preclinical models, lack of reliable biomarkers, and slow disease progression.
GNE 肌病，以前称为遗传性包涵体肌病（HIBM）或 Nonaka 肌病，是一种罕见的常染色体隐性肌肉疾病，其特征为进行性骨骼肌萎缩。其估计患病率为 1 比 900 万。GNE 肌病是由 GNE 基因突变引起的，该基因编码唾液酸生物合成的限速酶。该疾病的病理生理学尚未完全了解，但肌肉糖基化的低唾液酸化被认为起着重要作用。典型表现为双侧胫骨前肌无力引起的足下垂，发病于成年早期。疾病在接下来的几十年中缓慢进展，累及全身骨骼肌肉，股四头肌相对保留到疾病的晚期。在出现双侧足下垂的年轻成人中，应考虑 GNE 肌病的诊断。肌肉活检的组织病理学发现包括纤维大小变化、萎缩纤维、无炎症和改良 Gomori 三氯乙酸染色的特征性“镶边”空泡。通过在 GNE 基因的两个等位基因中存在致病性（主要是错义）突变来确诊。尽管这种疾病没有批准的治疗方法，但几种潜在治疗方法的临床前和临床研究正在进行中，包括底物替代和基于基因治疗的策略。然而，由于多种因素，包括疾病的罕见发病率、有限的临床前模型、缺乏可靠的生物标志物以及疾病进展缓慢，因此开发 GNE 肌病的治疗方法变得复杂。
