School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
School of Biotechnology, Jawaharlal Nehru University, New Delhi, India.
Neurol India. 2019 Sep-Oct;67(5):1213-1219. doi: 10.4103/0028-3886.271259.
Inherited neuromuscular diseases are a heterogeneous group of rare diseases for which the low general awareness leads to frequent misdiagnosis. Advances in DNA sequencing technologies are changing this situation, and it is apparent that these diseases are not as rare as previously thought. Knowledge of the pathogenic variants in patients is helping in research efforts to develop new therapies. Here we present a review of current knowledge in GNE myopathy, a rare neuromuscular disorder caused by mutations in the GNE gene that catalyzes the biosynthesis of sialic acid. The most common initial symptom is foot drop caused by anterior tibialis muscle weakness. There is a progressive wasting of distal skeletal muscles in the lower and upper extremities as well. The quadriceps is relatively spared, which is a distinguishing feature of this disease. The characteristic histological features include autophagic rimmed vacuoles with inclusion bodies. GNE variant analysis of Indian patients has revealed a founder mutation (p.Val727Met) common within the normal Indian populations, especially in the state of Gujurat. We discuss therapeutic options, including metabolite supplementation, pharmacological chaperones, and gene therapy. Initiatives that bring together patients, researchers, and physicians are necessary to improve knowledge and treatment for these rare disorders.
遗传性神经肌肉疾病是一组罕见疾病，由于普遍认识度低，导致误诊频繁。DNA 测序技术的进步正在改变这种情况，这些疾病显然不像以前认为的那么罕见。了解患者的致病性变异有助于开展研究工作，开发新的治疗方法。在这里，我们回顾了 GNE 肌病的现有知识，GNE 肌病是一种由 GNE 基因突变引起的罕见神经肌肉疾病，该基因催化唾液酸的生物合成。最常见的初始症状是胫骨前肌无力引起的足下垂。下肢和上肢的远端骨骼肌也会逐渐消瘦。股四头肌相对不受影响，这是该疾病的一个特征。其特征性组织学特征包括具有包涵体的自噬环空泡。对印度患者的 GNE 变异分析显示，一种常见的（p.Val727Met）突变是印度人群中的一个致病突变，特别是在古吉拉特邦。我们讨论了治疗选择，包括代谢物补充、药理学伴侣和基因治疗。为了提高对这些罕见疾病的认识和治疗，有必要将患者、研究人员和医生聚集在一起。
