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首页> 外文期刊>Neuromuscular disorders: NMD >Clinical and neuropathological features of X-linked spinal muscular atrophy (SMAX2) associated with a novel mutation in the UBA1 gene
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Clinical and neuropathological features of X-linked spinal muscular atrophy (SMAX2) associated with a novel mutation in the UBA1 gene

机译：X连锁性脊髓性肌萎缩症（SMAX2）与UBA1基因的新突变相关的临床和神经病理学特征

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Infantile-onset X-linked spinal muscular atrophy (SMAX2) is a rare lethal disorder linked to mutations in the UBA1 (previously UBE1) gene, encoding ubiquitin-activating enzyme 1 that has an important role in the ubiquitin-proteasome pathway. Published pathological reports are scarce. Here we report a male infant who presented from birth with predominantly truncal hypotonia following an antenatal history of reduced fetal movements. He had a myopathic face, profound weakness, multiple contractures and areflexia. Creatine kinase was moderately raised. Brain MRI showed non-specific symmetrical periventricular white matter changes. Neurophysiology revealed evidence of motor and sensory involvement and muscle biopsy showed marked inflammatory changes with subtle features suggestive of acute denervation. UBA1 sequencing revealed a novel hemizygous missense mutation (c.1670A>T; p.Glu557Val). He died from progressive respiratory failure at 4. months. On post mortem assessment, in addition to severe ventral motor neuron pathology, there was widespread involvement of the sensory system, as well as developmental and degenerative cerebellar abnormalities. In contrast to typical SMN1-associated SMA, the thalamus was unaffected. These findings indicate that SMAX2 is more accurately classified as a motor sensory neuronopathy rather than a pure anterior horn cell disorder. Ubiquitin-proteasome pathway defects may not only cause neurodegeneration but also affect normal neuronal development.
机译：婴儿期X连锁脊髓性肌萎缩症（SMAX2）是一种罕见的致死性疾病，与UBA1（先前为UBE1）基因的突变相关，该基因编码在泛素-蛋白酶体途径中起重要作用的泛素激活酶1。已发表的病理报告很少。在这里，我们报告了一名男婴，其出生后出现胎儿运动减少的病史后主要表现为截短性肌张力低下。他的脸有肌病，极度虚弱，有多个挛缩和反射力。肌酸激酶适度升高。脑MRI显示非特异性对称性脑室周围白质改变。神经生理学揭示了运动和感觉受累的证据，肌肉活检显示明显的炎症变化，并具有暗示急性神经支配的微妙特征。 UBA1测序揭示了一个新的半合子错义突变（c.1670A> T; p.Glu557Val）。他在4个月时因进行性呼吸衰竭死亡。验尸评估中，除了严重的腹侧运动神经元病理外，还广泛涉及感觉系统，发育和变性小脑异常。与典型的SMN1相关的SMA相反，丘脑不受影响。这些发现表明，SMAX2被更准确地分类为运动感觉神经病，而不是单纯的前角细胞疾病。泛素-蛋白酶体途径的缺陷不仅可能导致神经变性，而且会影响正常的神经元发育。

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