Department of Pediatrics, Peking University First Hospital, Beijing, China.
Department of Radiology, Peking University First Hospital, Beijing, China.
Pediatr Neurol. 2019 May;94:38-47. doi: 10.1016/j.pediatrneurol.2019.01.002. Epub 2019 Jan 8.
We aimed to delineate the pattern of natural course, neuroimaging features, and the genotypic spectrum of cavitating leukoencephalopathies.
Children (age of onset ≤16 years) who met the criteria for cavitating leukoencephalopathies from January 2009 to October 2018 were identified. Whole-exome sequencing and prospective follow-up study of the natural history and brain magnetic resonance imaging (MRI) were performed.
Thirty-seven children were clinically diagnosed with cavitating leukoencephalopathies. Pathogenic or likely pathogenic mutations in eight genes were identified in 31 individuals (83.78%): IBA57 (17/37), NDUFS1 (5/37), NDUFV1 (2/37), NDUFV2 (3/37), NDUFAF5 (1/37), LYRM7 (1/37), NDUFB8 (1/37), and GLRX5 (1/37). All genes were engaged in mitochondrial function. IBA57 was identified in half of children. Mutations in NDUFV2, NDUFAF5, NDUFB8, or GLRX5 were first found to be related to cavitating leukoencephalopathies. Follow-up with a median of 23.5 months (four to 107 months) was available. The median age at disease onset was 11 months. All cases presented acute or subacute onset, and the initial presentation was rapid motor regression in 35 cases. Thirty-five children (35/37) exhibited a stabilized or improved pattern. Cavities and high-intensity diffusion-weighted imaging signals were the common MRI features during the acute stage. Although clinically stable, 21 children had reserved high diffusion-weighted imaging signals for a long time. Patients with different gene mutations show different MRI patterns.
The study expands the number of genes involved in cavitating leukoencephalopathies to 22. IBA57 is the most common candidate gene. Most cases showed a stabilized or improved pattern after an acute or subacute onset, which is different from most other inherited metabolic diseases or leukodystrophies. More cases and a longer follow-up period are needed.
我们旨在描绘空泡性脑白质病变的自然病程、神经影像学特征和基因型谱。
从 2009 年 1 月至 2018 年 10 月，我们确定了符合空泡性脑白质病变标准的儿童（发病年龄≤16 岁）。对其进行全外显子组测序和前瞻性自然病史及脑磁共振成像（MRI）研究。
37 名儿童被临床诊断为空泡性脑白质病变。在 31 名个体中发现了 8 个基因的致病性或可能致病性突变（83.78%）：IBA57（17/37）、NDUFS1（5/37）、NDUFV1（2/37）、NDUFV2（3/37）、NDUFAF5（1/37）、LYRM7（1/37）、NDUFB8（1/37）和 GLRX5（1/37）。所有基因均参与线粒体功能。一半的儿童存在 IBA57 突变。NDUFV2、NDUFAF5、NDUFB8 或 GLRX5 的突变是首次被发现与空泡性脑白质病变有关。中位随访时间为 23.5 个月（4-107 个月）。疾病发病的中位年龄为 11 个月。所有病例均呈急性或亚急性起病，35 例初始表现为快速运动性倒退。35 名儿童（35/37）表现为稳定或改善的模式。在急性期，常见的 MRI 特征是空洞和高扩散加权成像信号。尽管临床稳定，但 21 名儿童的高扩散加权成像信号仍长时间保留。不同基因突变的患者表现出不同的 MRI 模式。
该研究将涉及空泡性脑白质病变的基因数量扩展到 22 个。IBA57 是最常见的候选基因。大多数病例在急性或亚急性发作后表现出稳定或改善的模式，这与大多数其他遗传性代谢疾病或脑白质营养不良不同。需要更多的病例和更长的随访时间。
