Redefining the phenotype of ALSP and AARS2 mutation-related leukodystrophy.
Redefining the phenotype of ALSP and AARS2 mutation-related leukodystrophy.
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DOI：
10.1212/nxg.0000000000000135
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发表时间：
2017-04
期刊：
影响因子：
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通讯作者：
Davagnanam I
中科院分区：
文献类型：
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作者：
Lakshmanan R;Adams ME;Lynch DS;Kinsella JA;Phadke R;Schott JM;Murphy E;Rohrer JD;Chataway J;Houlden H;Fox NC;Davagnanam I
概述2例临床、放射和病理相似的脑白质营养不良、成人起病的轴突球体和有色素性胶质细胞白质脑病(ALSP)和丙氨酰转移核糖核酸合成酶2突变相关脑白质营养不良(AARS2-L)的表型，并强调主要的鉴别特征。ALSP和AARS2-L病例是从我们研究所的成人起病的脑白质营养不良数据库中发现的。此外，通过文献回顾确定了有影像表现的病例。表型特征通过将已发表的病例与我们数据库中的病例相结合来确定。结合神经影像资料，对74例ALSP和10例AARS_2-L进行鉴别诊断。ALSP和AARS2-L的平均发病年龄分别为42岁和26岁。认知和运动症状是这两种疾病最常见的症状。卵巢衰竭仅见于AARS2-L，存在于所有已知的女性病例中。ALSP和AARS2-L均表现为融合的、不对称的、以额顶顶叶为主的脑室周围白质病变，皮质下U纤维稀少；累及锥体束和胼胝体；白质弥漫性改变，我们称之为“深层白质扩散点”。ALSP的中央萎缩和胼胝体变薄在ALSP中显著，而在AARS2-L中则不成比例地轻微。ALSP还偶尔显示脑室异常和额侧脑室周围白质钙化，这些特征在AARS2-L中未见。L显示脑白质稀疏，抑制液体衰减的反转恢复序列，这是ALSP中未见的特征。ALSP和AARS2-L具有相似的临床、影像和病理特征，我们已经强调了关键的鉴别特征。
To provide an overview of the phenotype of 2 clinically, radiologically, and pathologically similar leukodystrophies, adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and alanyl-transfer RNA synthetase 2 mutation–related leukodystrophy (AARS2-L), and highlight key differentiating features. ALSP and AARS2-L cases were identified from the adult-onset leukodystrophy database at our institution. In addition, cases with imaging findings were identified from a literature review. The phenotypic features were determined by combining published cases with those from our database. A combined total of 74 cases of ALSP and 10 cases of AARS2-L with neuroimaging data were identified. The mean age at onset was 42 years in ALSP and 26 years in AARS2-L. Cognitive and motor symptoms were the most common symptoms overall in both. Ovarian failure was exclusive to AARS2-L, present in all known female cases. Both ALSP and AARS2-L showed a confluent, asymmetric, predominantly frontoparietal, periventricular pattern of white matter disease with subcortical U-fiber sparing; pyramidal tract and corpus callosum involvement; and diffusion changes in the white matter which we have termed “deep white matter diffusion dots.” Central atrophy and corpus callosal thinning were prominent in ALSP and disproportionately mild in AARS2-L when present. ALSP also occasionally showed ventricular abnormalities and calcifications in the frontal periventricular white matter, features not seen in AARS2-L. AARS2-L demonstrates white matter rarefaction which suppresses on fluid-attenuated inversion recovery MRI sequences, a feature not seen in ALSP. ALSP and AARS2-L share similar clinical, imaging, and pathologic characteristics with key differentiating features that we have highlighted.