儿童X连锁血小板减少症3例及文献复习

Three cases report of X-linked thrombocytopenia and literature review

目的分析3例X连锁血小板计数减少症(XLT)患儿的临床和分子遗传学特征,提高该病的临床诊断水平。方法选择2012年1月至2014年5月于四川大学华西第二医院确诊为XLT的3例患儿为研究对象。本研究遵循的程序符合四川大学华西第二医院人体试验委员会所制定的伦理学标准,得到该委员会批准,分组征得受试对象监护人的知情同意,并与之签署临床研究知情同意书。结合国内外文献复习,对本组经WAS基因突变分析确诊的3例XLT患儿的临床特征和基因型进行回顾性分析。结果 3例(100.0%)XLT患儿均为男性,反复血小板计数减少为最突出临床表现,无阳性家族史,其确诊前均被误诊为原发性免疫性血小板减少症(ITP),使用糖皮质激素和静脉注射用免疫球蛋白(IVIG)治疗效果不佳,血小板计数持续减少。WAS基因分析证实患儿1和患儿3存在c.1378C>T错义突变,患儿2为c.256C>T错义突变,3例患者母亲均为相应突变基因携带者(100.0%)。结论 XLT为WAS的临床类型之一,以慢性或间歇性小血小板性血小板计数减少为显著临床特征,易于误诊为ITP。儿科医师对婴幼儿期起病的血小板计数减少的男性患儿应警惕XLT可能,并通过详尽病史采集、血小板计数和平均血小板体积(MPV)的动态监测,以及WAS基因突变检测,尽早明确诊断,指导临床治疗和预后评估。

Objective To further the understanding of the clinical features and molecular genetics of X-linked thrombocytopenia（XLT）,facilitating early diagnosis.Methods From January 2012 to May 2014,three children with XLT were included in the study.The study protocol was approved by the Ethical Review Board of Investigation in Human Being of West China Second University Hospital,Sichuan University.Informed consent was obtained from each participants′parents.The clinical data and genotypes of the three cases of XLT who were diagnosed by WASgene analysis were analyzed respectively.Results The 3cases（100.0%）with XLT were all boys characterized clinically by chronic or intermittent thrombocytopenia,without positive family history.Before definite diagnosis of XLT via WASgene mutation analysis,all 3cases were misdiagnosed as primary immune thrombocytopenia（ITP）and were given steroid and intravenous immunoglobulin（IVIG）therapies,but resulting in persistent or intermittent thrombocytopenia.WASgene mutation analysis revealed 2types of missense mutation,c.1378C〉T located in extron 11 of case 1and 3,while c.256C〉T located in extron 2of case 2.The mothers harbored the same respective WAS gene mutations.Conclusions XLT,a mild form of WAS,caused by WAS gene mutations,is clinically characterized by chronic or intermittent microthrombocytopenia and is easily be misdiagnosed as ITP.With high clinical alertness of XLT,pediatricians should always considering the diagnostic possibility of XLT when faced with boys presenting with thrombocytopenia during infancy and toddler period,particularly with poor therapeutic responses to conventional steroid or IVIG therapy.Early diagnosis could possibly be made based on elaborate history-taking,dynamic monitoring of platelet count and mean platelet volume（MPV）,WASgene mutation analysis which is of great importance for the clinical management and prediction of prognosis.