Objective To analyze the clinical and genetic features of four children with pediatric acute liver failure(PALF)caused by neuroblastoma-amplified sequence(NBAS)gene variant,as well as the correlation between clinical ...Objective To analyze the clinical and genetic features of four children with pediatric acute liver failure(PALF)caused by neuroblastoma-amplified sequence(NBAS)gene variant,as well as the correlation between clinical phenotype and genotype.Methods The clinical data and genetic test results of four children with NBAS gene variants admitted to the Department of Gastroenterology,Children's Hospital Affiliated to Zhejiang University School of Medicine from August 2015 to June 2023 mainly presenting with pediatric acuteliverfailure(PALF)were retrospectively analyzed.The relevant literature from January 2015 to May 2024 was retrieved using the Chinese and English keywords"NBAS,""neuroblastoma amplified sequence,""SOPH,""short stature with optic nerve atrophy and Pelger Huet anomaly,""liver failure,"and"neuroblastoma amplified sequence"indexed in the CNKI database,Wanfang Data Knowledge Service Platform,and PubMed database.The clinical features and gene mutation characteristics of domestic patients were summarized.Results The age at which the initial PALF attack occurred in the four children varied from eight months to three years and seven months.All patients developed PALF within 1-2 days after the onset of fever,with symptoms such as vomiting,convulsions,and mental depression or confusion,accompanied by a sharp increase in transaminases,elevated bilirubin and blood ammonia,hyperlactatemia,and hepatomegaly.The PALF gradually improved,and three pediatric patients showed extrahepatic manifestations following antipyretic,fluid replacement,and other symptomatic supportive treatment.Long-term follow-up showed that active temperature control and symptomatic therapy reduced the recurrence of PALF.Genetic testing identified eight kinds of NBASgenevariantssites.Family testing validated compound heterozygous variants,which included four missense variants,one nonsense variants,and three frameshift mutations.A literature study revealed that out of 51 Chinese patients with NBAS gene variants,98.0%(50/51)had liver involvement,and 37 cases showed PALF.A total of 61 mutation sites were identified,with c.3596G>A(45.1%,23/51)as a hotspot variants.Conclusion PALF caused by NBAS gene variant has obvious clinical and genetic characteristics,and there is a correlation between genotype and clinical phenotype.The c.3596G>A variant site is a hotspot mutation in China and is strongly correlated with the liver failure phenotype.展开更多
文摘Objective To analyze the clinical and genetic features of four children with pediatric acute liver failure(PALF)caused by neuroblastoma-amplified sequence(NBAS)gene variant,as well as the correlation between clinical phenotype and genotype.Methods The clinical data and genetic test results of four children with NBAS gene variants admitted to the Department of Gastroenterology,Children's Hospital Affiliated to Zhejiang University School of Medicine from August 2015 to June 2023 mainly presenting with pediatric acuteliverfailure(PALF)were retrospectively analyzed.The relevant literature from January 2015 to May 2024 was retrieved using the Chinese and English keywords"NBAS,""neuroblastoma amplified sequence,""SOPH,""short stature with optic nerve atrophy and Pelger Huet anomaly,""liver failure,"and"neuroblastoma amplified sequence"indexed in the CNKI database,Wanfang Data Knowledge Service Platform,and PubMed database.The clinical features and gene mutation characteristics of domestic patients were summarized.Results The age at which the initial PALF attack occurred in the four children varied from eight months to three years and seven months.All patients developed PALF within 1-2 days after the onset of fever,with symptoms such as vomiting,convulsions,and mental depression or confusion,accompanied by a sharp increase in transaminases,elevated bilirubin and blood ammonia,hyperlactatemia,and hepatomegaly.The PALF gradually improved,and three pediatric patients showed extrahepatic manifestations following antipyretic,fluid replacement,and other symptomatic supportive treatment.Long-term follow-up showed that active temperature control and symptomatic therapy reduced the recurrence of PALF.Genetic testing identified eight kinds of NBASgenevariantssites.Family testing validated compound heterozygous variants,which included four missense variants,one nonsense variants,and three frameshift mutations.A literature study revealed that out of 51 Chinese patients with NBAS gene variants,98.0%(50/51)had liver involvement,and 37 cases showed PALF.A total of 61 mutation sites were identified,with c.3596G>A(45.1%,23/51)as a hotspot variants.Conclusion PALF caused by NBAS gene variant has obvious clinical and genetic characteristics,and there is a correlation between genotype and clinical phenotype.The c.3596G>A variant site is a hotspot mutation in China and is strongly correlated with the liver failure phenotype.
