Lee Jin Sook, Lee Sangmoon, Choi Murim, Lim Byung Chan, Choi Jieun, Kim Ki Joong, Cheon Jung-Eun, Kim In-One, Chae Jong-Hee
Department of Pediatrics, Gachon Institute of Genome Medicine and Science, Gachon University Gil Medical Center, Incheon, South Korea.
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea.
Eur J Paediatr Neurol. 2017 Mar;21(2):404-409. doi: 10.1016/j.ejpn.2016.07.010. Epub 2016 Jul 18.
Vanishing white matter disease (VWM) is a chronic progressive leukoencephalopathy that is characterized by cerebellar ataxia and spasticity, together with cystic degeneration of the cerebral white matter as evidenced by brain magnetic resonance imaging (MRI). Here, we report two sisters with EIF2B2 variants, who presented with delayed development and failure to thrive before 1 year of age, developed cataracts, and showed diffuse leukoencephalopathy.
The index case had a history of hepatomegaly and intermittent vomiting after upper respiratory infection at 11 months of age. Her older brothers had died at an early age, one with similar symptoms and the other because of septic shock. Her older sister had similar presenting symptoms; she later suffered from both cataracts and primary amenorrhea, but showed neurological improvement. Her follow-up MRIs (at 21 years of age) revealed progressive diffuse brain atrophy with leukoencephalopathy, without cystic rarefaction. Whole-exome sequencing of the index case revealed the presence of the compound heterozygous variants, Val85Glu and Met226Lys in EIF2B2. The affected sister had the same compound heterozygous variants, and their unaffected parents were heterozygous carriers of each variant.
This study expanded the clinical and genetic spectrum of VWM with EIF2B2 variants. It would be better to consider VWM as an eIF2B-related multisystem disorder, not just as a neurological disorder, on the basis that this is a family of housekeeping genes that affect multiple organs.
消失性白质病（VWM）是一种慢性进行性白质脑病，其特征为小脑共济失调和痉挛，脑磁共振成像（MRI）显示脑白质呈囊性变性。在此，我们报告两名携带EIF2B2变异体的姐妹，她们在1岁前出现发育迟缓及生长发育不良，患有白内障，并表现出弥漫性白质脑病。
索引病例在11个月大时曾有肝肿大病史，上呼吸道感染后出现间歇性呕吐。她的哥哥早年去世，一个有类似症状，另一个死于感染性休克。她的姐姐有类似的症状表现；后来她同时患有白内障和原发性闭经，但神经功能有所改善。她的随访MRI（21岁时）显示进行性弥漫性脑萎缩伴白质脑病，无囊性稀疏。索引病例的全外显子组测序显示EIF2B2基因存在复合杂合变异体Val85Glu和Met226Lys。患病姐妹有相同的复合杂合变异体，未患病的父母分别是每个变异体的杂合携带者。
本研究扩展了携带EIF2B2变异体的VWM的临床和基因谱。鉴于这是一组影响多个器官的管家基因家族，最好将VWM视为一种与eIF2B相关的多系统疾病，而不仅仅是一种神经系统疾病。
