Department of Genetics & Molecular Medicine, Kamineni Hospitals, LB Nagar, Hyderabad, Telangana, India.
Department of Genetics, Osmania University, Tarnaka Hyderabad, Telangana, India.
J Child Neurol. 2020 May;35(6):393-397. doi: 10.1177/0883073820902308. Epub 2020 Feb 26.
Infection-induced acute encephalopathies (IIAEs) are a group of neurologic disorders caused post infection. They are of 8 types, 6 of which are herpes specific, whereas IIAE3 and IIAE4 can be triggered by infections additional to herpeslike influenza, enterovirus, etc. IIAE3 is also known as acute necrotizing encephalopathy type 1, which is a rare type of encephalopathy that occurs following an infection in infancy or early childhood. Symptoms include fever, cough, congestion, vomiting, and diarrhea followed by seizures, hallucination, ataxia, and abnormal muscle tone, and sometimes it leads to untimely death. Here, we describe a familial case where 3 siblings were clinically diagnosed with acute necrotizing encephalopathy 1. Genetic testing revealed 2 heterozygous variations: RANBP2 c.5249C>G, p.P1750 R, and CPT2 c.365C>T, p.S122F. Variants in and have been individually known to be associated with IIAE3 and IIAE4, respectively. Segregation analysis revealed that the RANBP2 variant was inherited from the father and the CPT2 variant from the mother. This case qualifies to be the first of its kind where digenic inheritance (ie, DNA sequence variants in 2 genes are required for the pathogenic phenotypes) appears to cause a lethal class of acute necrotizing encephalopathy.
感染诱导的急性脑病（IIAEs）是一组感染后引起的神经系统疾病。它们分为 8 种类型，其中 6 种是疱疹特异性的，而 IIAE3 和 IIAE4 除了疱疹样流感、肠道病毒等感染外也可引发。IIAE3 也称为急性坏死性脑病 1 型，是一种罕见的脑病，发生在婴儿期或幼儿期感染后。症状包括发热、咳嗽、鼻塞、呕吐和腹泻，随后出现癫痫发作、幻觉、共济失调和异常肌肉张力，有时会导致死亡。在这里，我们描述了一个家族性病例，3 个兄弟姐妹均被临床诊断为急性坏死性脑病 1 型。基因检测显示存在 2 种杂合变异：RANBP2 c.5249C>G，p.P1750R 和 CPT2 c.365C>T，p.S122F。和 分别与 IIAE3 和 IIAE4 相关。分离分析显示 RANBP2 变异来自父亲，CPT2 变异来自母亲。该病例是首例符合双基因遗传（即，2 个基因的 DNA 序列变异需要致病表型）的病例，似乎导致了一种致命性的急性坏死性脑病。
