本文關(guān)鍵詞： 噬血細胞綜合征 基因突變 臨床表現(xiàn)　出處：《遵義醫(yī)學院》2017年碩士論文　論文類型：學位論文

【摘要】：目的:了解本地區(qū)噬血細胞綜合征患兒HPS相關(guān)基因突變的發(fā)生率和類型,探討基因突變陽性和陰性患兒臨床特征及與預后的關(guān)系。方法:回顧性分析2014年1月至2017年1月遵義醫(yī)學院附屬醫(yī)院兒童血液腫瘤科住院治療的23例遵義地區(qū)噬血細胞綜合征患兒的臨床資料,根據(jù)HPS基因檢測結(jié)果,將患兒分為基因突變陽性組和基因突變陰性組,比較兩組患兒的發(fā)病年齡、性別,臨床癥狀、體征,各項實驗室指標及預后的差異。采用SPSS19.0對數(shù)據(jù)進行統(tǒng)計分析,運用單樣本Kolmogorov-Smirnov檢驗對數(shù)據(jù)進行正態(tài)性檢驗,Mann-Whitney U檢驗兩組間指標進行比較;分類計數(shù)資料組間比較采用Fisher確切概率檢驗(樣本量小于40);檢驗水準為P㩳0.05有統(tǒng)計學意義。結(jié)果:(1)56.5%(13/23)的患兒檢測出原發(fā)性噬血細胞綜合征的相關(guān)基因突變,基因突變檢出率由高到低依次為LYST(46.2%)、UNC13D(38.5%)、ITK(30.8%)、STXBP2(15.2%)和XIAP(7.7%),未見PRF1基因突變;(2)基因突變陽性組男7例,女6例,陰性組男6例,女4例,兩組患兒性別比較無統(tǒng)計學意義(P㧐0.05);(3)基因突變陽性組發(fā)病年齡4.12±4.68歲,陰性組5.82±4.16歲,兩組患兒發(fā)病年齡比較無統(tǒng)計學意義(P㧐0.05);(4)基因突變陽性組出現(xiàn)神經(jīng)系統(tǒng)癥狀2例(15.4%);陰性組出現(xiàn)神經(jīng)系統(tǒng)癥狀4例(40%),神經(jīng)系統(tǒng)受累例數(shù)在兩組患兒比較無統(tǒng)計學意義(P㧐0.05);(5)基因突變陽性組EB病毒感染陽性有4例(30.8%),肺炎支原體陽性4例(30.8%);陰性組EB病毒陽性有1例(10%),肺炎支原體陽性2例(20.0%);上述指標在兩組患兒比較均無統(tǒng)計學意義(P㧐0.05);(6)基因突變陽性組與陰性組出現(xiàn)外周血細胞兩系減少和低白蛋白血癥均為100%,基因突變陽性組NK細胞活性減低63.6%,SF升高500ug/L為92.3%,ALT升高≥40U/L為86.4%,LDH升高215 U/為92.3%,TG升高3.0mmo/L為53.8%,FIB1.5 g/L為76.9%,骨髓形態(tài)學檢查見噬血現(xiàn)象61.5%;陰性組NK細胞活性減低80%,SF升高500ug/L為80.0%,ALT升高≥40U/L為80.0%,LDH升高215 U/L為80.0%,TG升高3.0mmo/L為40.0%,FIB1.5 g/L為60.6%,骨髓形態(tài)學檢查見噬血現(xiàn)象40.0%,上述指標在兩組患兒比較均無統(tǒng)計學意義(P㧐0.05);將上述指標按診斷值分層后再次比較,各項指標亦無統(tǒng)計學意義(P㧐0.05);(7)基因突變陽性組存活7例,死亡6例,死亡率46.2%,基因突變陰性組存活9例,死亡1例,死亡率(10%),兩組患兒死亡率比較無統(tǒng)計學意義(P㧐0.05)。結(jié)論:(1)原發(fā)性噬血細胞綜合征相關(guān)突變基因在兒童HPS中的檢出率較高(56.5%),多為單基因或多基因的雜合突變,罕見純合基因突變者;(2)本地區(qū)的HPS患兒檢測到5種相關(guān)基因突變,分別是LYST、UNC13D、ITK、STXBP2和XIAP;其中LYST和UNC13D基因突變最常見,PRFI基因突變少見;(3)本研究中的部分突變基因致病意義不明確,但對存在細胞毒脫顆粒功能異常,尤其對存在家系遺傳,病情進展兇猛的患兒需警惕原發(fā)性HPS可能;(4)本研究中患兒的發(fā)病年齡、性別、病情嚴重程度,EB病毒感染率和預后等與具有相關(guān)基因突變無關(guān)。
[Abstract]:Objective: to investigate the incidence and type of HPS related gene mutations in children with hemophagocytic syndrome. To investigate the relationship between clinical features and prognosis of children with gene mutation positive and negative. Methods:. The clinical data of 23 children with hemophagocytic syndrome in Zunyi district were retrospectively analyzed from January 2014 to January 2017 in Department of Blood Oncology, affiliated Hospital of Zunyi Medical College. According to the results of HPS gene detection, the children were divided into two groups: gene mutation positive group and gene mutation negative group. The age, sex, clinical symptoms and signs of the two groups were compared. SPSS19.0 was used to analyze the data, and single sample Kolmogorov-Smirnov test was used to test the normality of the data. The indexes of Mann-Whitney U test were compared between the two groups. The Fisher exact probability test was used to compare the classified counting data (sample size less than 40). The test level is P? Results the mutation of gene related to primary hemophagocytic syndrome was detected in 56.5% of the children with primary hemophagocytic syndrome (13 / 23). The detection rate of gene mutation from high to low was as follows: LYST 46.2 and UNC13D5 / 38.5ITK 30.8). STXBP215.2) and XIAP 7.7G, no mutation of PRF1 gene was found. 2) there were 7 males, 6 females, 6 males and 4 females in the gene mutation positive group. There was no significant difference in sex between the two groups. The age of onset was 4.12 鹵4.68 years in the positive group and 5.82 鹵4.16 years in the negative group. 0.05; (4) there were 2 cases with nervous system symptoms in the positive group of gene mutation. In the negative group, there were 4 cases with nervous system symptoms. There were no significant differences between the two groups in the number of cases of nervous system involvement in the two groups. 0.05; 5) Epstein-Barr virus (EBV) infection was found in 4 cases of positive mutation and mycoplasma pneumoniae was found in 4 cases (30.8%) and mycoplasma pneumoniae in 4 cases (30.8%). In negative group, 1 case was positive for EB virus and 2 cases were positive for Mycoplasma pneumoniae. There was no significant difference in the above indexes between the two groups. 0.05; (6) the number of peripheral blood cells decreased and hypoalbuminemia in both positive and negative groups were 100, and NK cell activity decreased by 63.6% in positive mutation group. The elevation of SF by 500ugr / L was 92.3U / L, the elevation of alt 鈮，

本文編號：1450756