儿童反复发热相关急性肝衰竭的诊治

李忠蝶; 黎佳琪; 库尔班江·阿布都西库尔

doi:10.3969/j.issn.1001-5256.2022.02.003

儿童反复发热相关急性肝衰竭的诊治

DOI: 10.3969/j.issn.1001-5256.2022.02.003

复旦大学附属儿科医院肝病科, 上海 201102

利益冲突声明：所有作者均声明不存在利益冲突。

作者贡献声明：李忠蝶、黎佳琪及库尔班江·阿布都西库尔负责收集资料并撰写文章；库尔班江·阿布都西库尔负责拟定写作思路, 指导撰写并最后定稿。

详细信息

通信作者:
库尔班江·阿布都西库尔, k_abuduxikuer@fudan.edu.cn

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出版历程
- 收稿日期: 2021-12-17
- 录用日期: 2021-12-20
- 出版日期: 2022-02-20

Diagnosis and treatment of fever-related recurrent acute liver failure in children

Department of Hepatology, Children's Hospital of Fudan University, Shanghai 201102, China

More Information

Corresponding author: ABUDUXIKUER Kuerbanjiang, k_abuduxikuer@fudan.edu.cn

摘要

摘要: 婴儿及儿童急性肝衰竭是严重危及生命的疾病, 病因复杂。反复发作的急性肝衰竭(RALF)是指出现两次或两次以上急性肝损伤且至少有一次达到肝衰竭的诊断标准。RALF患儿在急性肝损伤发病间期生化指标可完全恢复正常。临床上RALF患儿病因除了感染、免疫、药物及毒物等因素, 还有遗传性或代谢性疾病。部分遗传性肝病引起的RALF每次发作均与发热相关。本文讨论了NBAS、SCYL1及RINT1等基因缺陷病导致的反复发热相关急性肝衰竭诊治。
- 肝功能衰竭, 急性 /
- 发热 /
- 遗传性疾病, 先天性
Abstract: Acute liver failure (ALF) in infants and children is a severe life-threatening disease caused by multiple etiologies. Recurrent acute liver failure (RALF) is defined as the occurrence of acute liver injury two or more times, with at least one episode meeting the diagnostic criteria for ALF. Biochemical parameters usually return to normal between acute liver injury episodes in children with RALF. Clinical etiologies of RALF include infections, immunologic disorders, drug, and toxin, as well as hereditary or metabolic disorders, and some episodes of RALF caused by hereditary liver disorders are always associated with fever. This article discusses the diagnosis and treatment of fever-related RALF caused by genetic defects of NBAS, SCYL1, and RINT1.
- Liver Failure, Acute /
- Fever /
- Genetic Diseases, Inborn

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表 1 反复发热相关急性肝衰竭特点

项目	NBAS缺陷病	SCYL1缺陷病	RINT1缺陷病
相关基因	NBAS基因, 位于染色体2p24.3区域	SCYL1基因, 位于染色体11q13.1区域	RINT1基因, 位于染色体7q22.3区域
蛋白功能及可能的发病机制	NBAS蛋白作为突触融合蛋白18复合体的一个亚基, 在高尔基体到内质网的逆向运输及无义介导的mRNA降解通路中发挥重要作用：既能使目标信使RNA降解, 又能调节基因的转录表达, 同时还在胚胎形成中发挥作用。NBAS基因在人体很多组织中广泛表达, 并且影响到1444种基因的表达, 其目标基因很多都与骨盐沉积和发育、胆固醇合成以及淋巴细胞异常有关	SCYL1蛋白通过与膜层蛋白复合体1相连, 可在高尔基体到内质网的逆向运输及调节高尔基体稳态中发挥重要作用。另外, SCYL1也可通过作用于核孔复合物促进细胞核RNA运输至细胞浆	RINT1蛋白与NBAS及UVRAG等蛋白相互作用, 促进高尔基体至内质网逆向囊泡运输。当营养缺乏或感染时高尔基体至内质网逆向囊泡运输受到抑制、激活细胞自噬反应。RINT1基因突变最终导致细胞自噬异常造成肝脏和骨骼病变
肝脏表型	反复发热相关急性肝衰竭、持续转氨酶升高、胆汁淤积症、肝肿大	反复发热相关急性肝衰竭、肝肿大、脾肿大	新生儿黄疸、反复发热相关急性肝衰竭、肝功能指标异常、肝肿大、脾肿大
肝脏病理	脂肪肝、肝细胞肿胀、中央静脉周围性肝纤维化、胆管增生、非特异性炎症	肝纤维化、胆汁淤积、胆管反应、脂肪变性	肝纤维化、脂肪变性、Kupffer细胞增生
肝外表现	SOPH综合征、骨密度减低、前囟门闭合延迟、脊柱异常、运动或智力发育落后、皮肤松弛、IgG水平下降、NK细胞减少、肌张力低下、骨骼肌萎缩	发育迟缓(运动、智力或语言)、周围神经病变、小脑萎缩和共济失调、小头畸形、神经性口吃、近端肌无力、手足肌肉萎缩、马蹄内翻足、枕大池囊肿	早产、低血糖、矮小病、马蹄内翻足、椎骨发育不良、喙型椎骨、椎骨形态不规则、扁椎骨、髋臼异常、股骨头骨骺异常
基因型-表型相关性	存在基因型-表型相关性, 携带严重突变和错义突变/非框移缺失或重复突变时, 错义或非框移变异在NBAS蛋白上的位置决定了患者的主要临床表现	尚不清楚	尚不清楚

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