成人原发性噬血细胞综合征一例报告及文献复习

A case report of adult onset of primary hemophagocytic syndrome with literature review

目的探讨成人原发性噬血细胞综合征（HPS）的诊断要点、成人患者基因表型特点与疾病发生的关系。方法对1例根据HLH-2004诊断标准确诊的成人HPS患者临床特点进行分析，并采用聚合酶链反应检测穿孔素基因（PRF1）、STX11、UNC13D、SH2D1A和RAB27A基因序列并探讨其发病机制。结果确诊病例为48岁男性患者，表现为反复发热、全血细胞减少伴淋巴结肿大，骨髓中存在噬血现象、血清铁蛋白升高（2000μg／L）、NK细胞活性下降（20．13％）、可溶性CD25升高（1227．7万U／L），根据HLH-2004诊断标准确诊为HPS。患者存在病毒感染，未找到其他可能引起HPS的疾病，予抗病毒治疗效果不佳。最终经基因测序证实为PRFl基因突变的原发性HPS。结论原发性HPS虽多见于婴幼儿，但青少年及成年仍有发病可能，对病情反复发作、原发病不明的患者进行基因筛查十分必要。分子遗传学改变是鉴别原发性和获得性HPS的关键。

Objective To introduce the clinical manifestations and laboratory tests of adult onset of primary hemophagocytic syndrome （ HPS）, and to investigate the essentials of diagnosis and the genotype characteristics in adult onset patient. Methods The definite diagnosis of HPS was made according to HLH- 2004. Exons of PRF1, STXll, UNC13D, SH2D1A and RAB27A genes coding region were amplified using polymerase chain reaction. Results A 48-year-old man was admitted to our hospital because of recurrent fe- ver, pancytopenia and lymph node enlargement. His laboratory test revealed bone marrow hemophagocytosis, elevated ferritin level （2000 μg/L） , reduced level of NK cell activity （20.13%） and elevated soluble CD25 level （ 12277 U/ml）. Based on the HLH-2004 diagnostic criteria, the patient was diagnosed as HPS. The patient had viral infection, and no other primary disease was identified that would cause HPS. The patient re- sponded poorly to anti-viral therapy. DNA sequencing was used to confirm that perforin gene mutations might be one of the causes of the patient suffered from primary HPS. Conclusions Although primary HPS usually affects infants and young children, it also occurred in teens and adults. It is essential to perform genetic screenings to patient whose illnesses recur with unknown causes. In addition, detection of molecular genetic alterations can be used to distinguish primary HPS from acquired HPS.