1例ILFS2患儿临床与免疫学特征研究

目的探讨1例由NBAS(neuroblastoma amplified sequence,NBAS)基因缺陷导致的婴儿肝功能衰竭综合征2型(infantile liver failure syndrome 2,ILFS2)患儿的临床特征、免疫表型、诊疗措施并总结相关文献报道。方法对1例临床表现为反复发热伴急性肝功能衰竭患儿行免疫学初筛、免疫相关基因测序、外周血涂片找P-H细胞;淋巴细胞各亚群分析及增殖功能、NK细胞免疫功能评估。总结已报道NBAS基因缺陷导致ILFS2患儿的临床特征、免疫学表型及诊疗方法。结果 1)确诊1例NBAS基因复合杂合变异致ILFS2患儿(c.67516754delCTCC]、c.3596-G>A]),外周血涂片可见典型Pelger-Hu?t细胞,患儿NK细胞数量及比率均减少,NK细胞杀伤活性明显降低,淋巴细胞增殖功能无异常。2)文献检索纳入已报道的22例ILFS2患儿,所有患儿肝内表型均为发热引起反复急性肝功能衰竭(recurrent acute liver failure,RALF),而肝外表型各不相同,如轻微脑萎缩、身材矮小、Pelger-Hu?t细胞阳性、眼距过窄、慢性病毒感染、NK细胞减少、低丙种球蛋白血症等。结论确诊1例NBAS基因变异致ILFS2患儿,患儿存在NK细胞数量及功能缺陷。ILFS2的确诊依赖临床表现及基因检测,免疫功能筛查亦有助于诊断。早期及时控制体温对于预防及改善预后十分关键。

Clinical and immunological characteristics of a case with ILFS2

This study was performed to investigated the clinical features, immunophenotype, diagnostic and therapeutic approach of recurrent acute liver failure caused by neuroblastoma amplified sequence(NBAS) gene defects in a child. Clinical characteristics, immunologic screening, high-throughput sequencing of immune-related genes, Pelger-Hu?t cells in the peripheral blood, lymphocyte proliferation and NK cell function were analyzed in the patient with recurrent acute liver failure due to fever. The related literature was searched by using search terms‘NBAS’. Data indicated a final diagnosis of infantile liver failure syndrome 2(ILFS2), which caused by a novel compound heterozygous mutation(c.67516754 delCTCC] and c.3596-G>A]) in NBAS gene;Pelger-Hu?t cells are existed in the peripheral blood. The patient presented with lower NK count and cytotoxic index, and normal proliferation of B cell and T cell. A total of 4 literatures were enrolled for analysis, in which 22 patients with NBAS gene compound heterozygous mutation suffered recurrent acute liver failure. The phenotypic variability of these patients highlighted that the mutations in NBAS lead to a clinical spectrum ranging from isolated RALF to a multisystemic phenotype including short stature, hypotelorism, Pelger-Hu?t cells anomaly, skeletal dysplasia, chronic viral infection, reduced natural killer cells, hypogammaglobulinemia and so on. In conclusion a case of ILFS2 with lower NK count and cytotoxic index has diagnosed by gene sequencing and immunophenotype analysis. Early and effective control of fever often allows prevention of liver crises.