Defective GNE causes sialuria, NK and IBM2

Sialuria (MIM:269921) is caused by a metabolic defect where the UDP?N?acetylglucosamine 2?epimerase, N?acetylmannosamine kinase (GNE) gene lacks feedback inhibition resulting in constitutive overproduction of free sialic acid (Neu5Ac) (Montreuil et al. 1968, Fontaine et al. 1968). Sialuria is characterised by a large cytoplasmic accumulation and urinary excretion of Neu5Ac (Kamerling et al. 1979). Sialurias differ from sialidoses, in which there is storage and excretion of 'bound' Neu5Ac. Defects in GNE also cause Nonaka myopathy (NK; MIM:605820), an early adult-onset disorder characterised by muscle weakness and wasting of distal muscles, especially the anterior tibial muscles (Nonaka et al. 1981, Asaka et al. 2001). Defects in GNE also cause inclusion body myopathy 2 (IBM2; MIM:600737), an autosomal recessive disorder with a similar phenotype to Nonaka myopathy (NK). IBM2 is an adult-onset, proximal and distal muscle weakness and wasting disorder. Muscle biospsy reveals from sufferers shows a rimmed vacuole myopathy and the degenerating muscle fibers contained abnormal amounts of beta-amyloid protein such as that found in neurodegenerative diorders. However, there is no neurological symptoms in these patients (Argov & Yarom 1984).

Sialuria（MIM:269921）由代谢缺陷引起，该缺陷导致UDP-N-乙酰葡萄糖胺2-表异构酶、N-乙酰甘露糖胺激酶（GNE）基因缺乏反馈抑制，从而导致游离唾液酸（Neu5Ac）的持续过度生产（Montreuil 等，1968年，Fontaine 等，1968年）。Sialuria 以胞浆内大量积累和尿液中唾液酸（Neu5Ac）的排泄为特征（Kamerling 等，1979年）。Sialuria 与唾液酸酶病不同，后者表现为‘结合’唾液酸（Neu5Ac）的储存和排泄。GNE 基因的缺陷还导致 Nonaka 肌病（NK；MIM:605820），一种以肌肉无力、尤其是前胫骨肌肉萎缩为特征的成年早期发病疾病（Nonaka 等，1981年，Asaka 等，2001年）。GNE 基因的缺陷还导致包含体肌病2（IBM2；MIM:600737），一种与 Nonaka 肌病（NK）具有相似表型的常染色体隐性遗传疾病。IBM2 是一种成年发病、近端和远端肌肉无力和萎缩疾病。肌活检显示受影响者的肌肉中出现带状空泡肌病，其中退化的肌纤维含有异常量的β-淀粉样蛋白，类似于在神经退行性疾病中发现的情况。然而，这些患者没有神经系统症状（Argov & Yarom，1984年）。