DARS相关的白质脑病可模仿类固醇反应性神经炎症性疾病。
DARS-associated leukoencephalopathy can mimic a steroid-responsive neuroinflammatory disorder.
作者信息
Wolf Nicole I, Toro Camilo, Kister Ilya, Latif Kartikasalwah Abd, Leventer Richard, Pizzino Amy, Simons Cas, Abbink Truus E M, Taft Ryan J, van der Knaap Marjo S, Vanderver Adeline
机构信息
From the Department of Child Neurology (N.I.W., T.E.M.A., M.S.v.d.K.), VU University Medical Center, Amsterdam; the Neuroscience Campus Amsterdam (N.I.W., T.E.M.A., M.S.v.d.K.), the Netherlands; the NIH Undiagnosed Diseases Program (C.T.), National Institutes of Health, Bethesda, MD; the NYU Multiple Sclerosis Center (I.K.), Department of Neurology, NYU School of Medicine, New York; the Department of Radiology (K.A.L.), Hospital Kuala Lumpur, Malaysia; the Department of Neurology (R.L.), Royal Children's Hospital; Murdoch Children's Research Institute (R.L.); the Department of Pediatrics (R.L.), University of Melbourne, Australia; the Department of Neurology (A.P., A.V.), Children's National Medical Center, Washington, DC; the Institute for Molecular Bioscience (C.S., R.J.T.), University of Queensland, St Lucia, Queensland, Australia; the Departments of Integrative Systems Biology and Pediatrics (R.J.T.), George Washington University School of Medicine, Washington, DC; Illumina Inc. (R.J.T.), San Diego, CA; and the Department of Functional Genomics (M.S.v.d.K.), Center for Neurogenomics and Cognitive Research, VU University, Amsterdam, the Netherlands.
出版信息
Neurology. 2015 Jan 20;84(3):226-30. doi: 10.1212/WNL.0000000000001157. Epub 2014 Dec 19.
OBJECTIVE
To describe the expanding clinical spectrum of a recently described hereditary leukoencephalopathy, hypomyelination with brainstem and spinal cord involvement and leg spasticity, which is caused by mutations in the aspartyl tRNA-synthetase encoding gene DARS, including patients with an adolescent onset.
METHODS
Three patients with mutations in DARS were identified by combining MRI pattern recognition and genetic analysis.
RESULTS
One patient had the typical infantile presentation, but 2 patients with onset in late adolescence had a disease mimicking an acquired inflammatory CNS disorder. Adolescent-onset patients presented with subacute spastic paraplegia and had positive response to steroids. They had only minor focal supratentorial white matter abnormalities, but identical spinal cord changes involving dorsal columns and corticospinal tracts. Clinical presentation included subacute spastic paraplegia with partial improvement on steroids.
CONCLUSIONS
Focal T2 hyperintense white matter changes on brain MRI in combination with spinal cord signal abnormalities usually suggest acquired inflammatory conditions such as multiple sclerosis, especially in the context of relapsing course and a positive response to steroid treatment. Adolescents with mutations in DARS can present with a comparable clinical picture, broadening the clinical spectrum of hypomyelination with brainstem and spinal cord involvement and leg spasticity.
目的
描述一种最近被描述的遗传性白质脑病的不断扩大的临床谱，即伴有脑干和脊髓受累及腿部痉挛的髓鞘形成不足，其由天冬氨酰tRNA合成酶编码基因DARS突变引起，包括青少年起病的患者。
方法
通过结合MRI模式识别和基因分析，鉴定出3例DARS基因突变患者。
结果
1例患者具有典型的婴儿期表现，但2例青春期晚期起病的患者有一种类似获得性炎症性中枢神经系统疾病的病症。青春期起病的患者表现为亚急性痉挛性截瘫，对类固醇治疗有阳性反应。他们仅在幕上脑白质有轻微局灶性异常，但脊髓有相同改变，累及后索和皮质脊髓束。临床表现为亚急性痉挛性截瘫，类固醇治疗后部分改善。
结论
脑部MRI上局灶性T2高信号白质改变伴脊髓信号异常通常提示获得性炎症性疾病，如多发性硬化，特别是在复发病程和对类固醇治疗有阳性反应的情况下。DARS基因突变的青少年可表现出类似的临床症状，拓宽了伴有脑干和脊髓受累及腿部痉挛的髓鞘形成不足的临床谱。
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