Objective: To analyze the clinical and genetic features of pediatric acute liver failure (PALF) caused by neuroblastoma-amplified sequence (NBAS) gene variants and to investigate the correlation between clinical phenotypes and genotypes. Methods: A retrospective analysis was conducted on the clinical data and genetic test results of 4 pediatric patients with NBAS gene variants presenting primarily with PALF, who were admitted to the Department of Gastroenterology at the Children's Hospital of Zhejiang University School of Medicine from August 2015 to June 2023. A literature review was performed using the keywords "NBAS", "neuroblastoma amplified sequence", "SOPH", "short stature with optic nerve atrophy and Pelger-Huët anomaly", "liver failure", and "neuroblastoma amplified sequence" in both Chinese and English, searching the CNKI, Wanfang Data Knowledge Service Platform, and PubMed databases for articles published from January 2015 to May 2024. The clinical features and genetic characteristics of domestic patients were summarized. Results: The age of first onset of PALF in the 4 patients ranged from 8 months to 3 years and 7 months. All patients developed PALF within 1-2 d after the onset of fever, with symptoms including vomiting, seizures, lethargy, or altered consciousness, accompanied by a sharp increase in transaminases, elevated bilirubin and blood ammonia, hyperlactatemia, and hepatomegaly. After antipyretic therapy, fluid supplementation, and other symptomatic supportive treatments, the PALF gradually improved in all patients, with 3 patients also exhibiting extrahepatic symptoms. Long-term follow-up showed that active temperature control and symptomatic management could reduce the recurrence of PALF. Genetic testing identified 8 NBAS gene variants sites, all confirmed as compound heterozygous mutations through family verification, including 4 missense mutations, 1 nonsense mutation, and 3 frameshift mutations. A literature review included 51 cases of domestic NBAS gene mutations, revealing that 98.0% (50/51) of patients had liver involvement, with 35 cases presenting as PALF. A total of 61 variant sites were identified, with c.3596G>A (45.1%, 23/51) being the most common hotspot mutation. Conclusions: NBAS gene mutations leading to PALF have distinct clinical and genetic characteristics, with a correlation between genotype and clinical phenotype. The c.3596G>A mutation is a hotspot variant in domestic patients and is strongly associated with the liver failure phenotype.
目的： 分析神经母细胞瘤扩增序列（NBAS）基因变异致儿童急性肝功能衰竭患儿的的临床和遗传学特征，并分析其临床表型与基因型的相关性。 方法： 回顾性分析2015年8月至2023年6月在浙江大学医学院附属儿童医院消化科收治的4例以儿童急性肝功能衰竭（PALF）为主要表现的NBAS基因变异患儿的临床资料及基因检测结果。以“NBAS”“neuroblastoma amplified sequence”“SOPH”“short stature with optic nerve atrophy and Pelger-Huët anomaly”和“肝衰竭”“神经母细胞瘤扩增序列”为中英文关键词，检索2015年1月至2024年5月的中国知网数据库、万方数据知识服务平台和PubMed数据库收录的相关文献，总结国内患者的临床特征和基因变异特点。 结果： 4例患儿的PALF首次发作年龄为8个月至3岁7个月。所有患儿在发热后1～2 d内出现PALF，症状包括呕吐，抽搐，精神萎靡或神志不清等，伴随转氨酶急剧上升，胆红素和血氨升高，高乳酸血症和肝脏肿大。经过退热、补液及其他对症支持治疗后，患儿的PALF逐渐好转，其中3例还表现出肝外症状。长期随访显示，通过积极的体温控制和对症处理，可减少PALF的反复发作。基因检测共发现8种NBAS基因变异位点，经家系验证均为复合杂合变异，包括4种错义变异、1种无义变异和3种移码变异。文献回顾共纳入51例国内NBAS基因变异陷患者，发现98.0%（50/51）的患者存在肝脏受累，其中35例表现为PALF。共发现61种变异位点，其中c.3596G>A（45.1%，23/51）为热点变异。 结论： NBAS基因变异导致的PALF具有明显的临床和遗传学特征，且存在基因型与临床表型的相关性，其中c.3596G>A变异位点在国内为热点变异，与肝衰竭表型有较强的关联性。.