NBAS基因突变所致婴儿肝功能衰竭综合征2型病例临床特点及基因分析

Clinical characteristics and genetic analysis of type 2 cases of infantile liver failure syndrome caused by NBAS gene mutation and literature review

目的分析NBAS基因突变所致2例儿童急性肝衰竭患儿的临床和遗传学特点。方法回顾性分析安徽省儿童医院2018年12月收治的2例NBAS基因突变所致婴儿肝功能衰竭综合征2型的患儿临床和遗传学特点进行总结分析。结果共2例(例1例2)均为女性,发病年龄1岁4月~3岁。2例患儿均在发热后出现急性肝衰竭和(或)复发性肝酶增高或表现。2例发热后口服对乙酰氨基酚退热(累计剂量20~35 mg/kg)。例2经治疗后肝酶恢复正常,发病间期无特殊,近半年未再发作。例1体温控制不理想,出现凝血功能、高氨血症以及低血糖等不可逆性肝衰竭而死亡。2例患儿均为NBAS基因复合杂合变异所致婴儿肝功能衰竭综合征2型。结论NBAS基因突变引起的临床表型范围广,从孤立的复发性肝酶增多/急性肝衰竭到SOPH综合征的多系统疾病。对存在治疗剂量对乙酰氨基酚暴露史的肝衰竭患儿,除药物因素,应考虑其他遗传性病因。

Objective To analyze the clinical and genetic characteristics of 2 children with acute liver failure caused by NBAS gene mutation.Methods A retrospective analysis of the clinical and genetic characteristics of 2 children with infant liver failure syndrome type 2 caused by NBAS gene mutations admitted to XX Hospital in December 2018 was summarized and analyzed.Results A total of 2 cases(case 1 and case 2)were all females,and the age of onset was 1 year and 4 months to 3 years.Both children had acute liver failure and/or recurrent liver enzyme increase or manifestations after fever.Two patients took acetaminophen to relieve fever after fever(cumulative dose 20~35 mg/kg).The liver enzymes of case 2 returned to normal after treatment,there was no special interval of onset,and no recurrence occurred in the past six months.Case 1 had poor temperature control,and died of irreversible liver failure such as blood coagulation,hyperammonemia,and hypoglycemia.Both cases were infant liver failure syndrome type 2 caused by compound heterozygous mutation of NBAS gene.Conclusion NBAS gene mutations cause a wide range of clinical phenotypes,ranging from isolated recurrent liver enzyme hyperenzymes/acute liver failure to multi-system diseases such as SOPH syndrome.For children with liver failure who have a history of exposure to therapeutic doses of acetaminophen,in addition to drug factors,other genetic causes should be considered.