Nishino Ichizo, Carrillo-Carrasco Nuria, Argov Zohar
Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan.
Therapeutics for Rare and Neglected Diseases, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland, USA.
J Neurol Neurosurg Psychiatry. 2015 Apr;86(4):385-92. doi: 10.1136/jnnp-2013-307051. Epub 2014 Jul 7.
GNE myopathy is an autosomal recessive muscle disease caused by biallelic mutations in GNE, a gene encoding for a single protein with key enzymatic activities, UDP-N-acetylglucosamine 2-epimerase and N-acetylmannosamine kinase, in sialic acid biosynthetic pathway. The diagnosis should be considered primarily in patients presenting with distal weakness (foot drop) in early adulthood (other onset symptoms are possible too). The disease slowly progresses to involve other lower and upper extremities' muscles, with marked sparing of the quadriceps. Characteristic findings on biopsies of affected muscles include 'rimmed' (autophagic) vacuoles, aggregation of various proteins and fibre size variation. The diagnosis is confirmed by sequencing of the GNE gene. Note that we use a new mutation nomenclature based on the longest transcript (GenBank: NM_001128227), which encodes a 31-amino acid longer protein than the originally described one (GenBank: NM_005476), which has been used previously in most papers. Based upon the pathophysiology of the disease, recent clinical trials as well as early gene therapy trials have evaluated the use of sialic acid or N-acetylmannosamine (a precursor of sialic acid) in patients with GNE myopathy. Now that therapies are under investigation, it is critical that a timely and accurate diagnosis is made in patients with GNE myopathy.
GNE肌病是一种常染色体隐性肌肉疾病，由GNE基因的双等位基因突变引起。GNE基因编码一种具有关键酶活性的单一蛋白质，即唾液酸生物合成途径中的UDP-N-乙酰葡糖胺2-表异构酶和N-乙酰甘露糖胺激酶。诊断主要应考虑在成年早期出现远端肌无力（足下垂）的患者中（也可能有其他起病症状）。疾病缓慢进展，累及其他下肢和上肢肌肉，股四头肌明显不受累。受累肌肉活检的特征性发现包括“镶边”（自噬）空泡、各种蛋白质聚集和纤维大小变异。通过对GNE基因进行测序来确诊。请注意，我们使用基于最长转录本（GenBank：NM_001128227）的新突变命名法，该转录本编码的蛋白质比最初描述的（GenBank：NM_005476）长31个氨基酸，之前大多数论文都使用的是后者。基于该疾病的病理生理学，近期的临床试验以及早期基因治疗试验评估了在GNE肌病患者中使用唾液酸或N-乙酰甘露糖胺（唾液酸的前体）的情况。鉴于正在对治疗方法进行研究，对GNE肌病患者进行及时、准确的诊断至关重要。
