Caseinolytic peptidase B homolog (CLPB) is a mitochondrial protein which is highly expressed in brain. Its deficiency may be associated with severe neonatal encephalopathy. This report describes a case of fatal neonatal encephalopathy associated with biallelic stop-gain mutation in CLPB (NM_001258392.3:c.1159C>T/p.Arg387*). Neurologic disorder encompasses pre- and post-natal features including polyhydramnios, intrauterine growth restriction, respiratory insufficiency, lethargy, excessive startle reflex, generalized hypertonia, and epileptic seizures. Brain macroscopic examination demonstrates frontal severe periventricular cystic leukoencephalopathy, along with mild ex-vacuo tri-ventricular dilatation. The most striking immunohistopathologic features are striato-thalamic neurodegeneration and deep white matter loss associated with strong reactive astrogliosis. This report supports that CLPB deficiency should be considered among the neurometabolic disorders associated with severe prenatal-onset neurologic impairment that may result from cystic leukoencephalopathy.

中文翻译：

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CLPB 缺乏相关的新生儿空洞性白质脑病：神经系统疾病的潜在病理机制。

酪蛋白分解肽酶 B 同源物 (CLPB) 是一种在大脑中高度表达的线粒体蛋白。它的缺乏可能与严重的新生儿脑病有关。本报告描述了一例与 CLPB 中双等位基因停止增益突变相关的致命性新生儿脑病 (NM_001258392.3:c.1159C>T/p.Arg387*)。神经系统疾病包括产前和产后特征，包括羊水过多、子宫内生长受限、呼吸功能不全、嗜睡、惊跳反射过度、全身张力亢进和癫痫发作。脑肉眼检查显示额叶严重的脑室周围囊性白质脑病，以及轻度的非真空三脑室扩张。最显着的免疫组织病理学特征是纹状体丘脑神经变性和与强反应性星形胶质细胞增生相关的深部白质损失。该报告支持 CLPB 缺乏应被视为与可能由囊性白质脑病引起的严重产前神经功能障碍相关的神经代谢紊乱。