Clinical Significance Of Detection Of Genes Associated With Hemophagocytic Syndrome In Children

Objective: To understand the incidence and type of mutations in hemophagocytic syndrome in children with HPS in order to know the relationship in clinical aspects and prognosis among children with or without gene mutations.Methods: Retrospective analysis of 23 cases of children with the clear diagnosis of hemophagocytic syndrome(HPS)in the Children Department of Hematology of Affiliated Hospital of Zunyi Medical College from January 2014 to January 2017,clinical information were collected including gender,age,clinical symptoms,signs,laboratory indicators,prognosis and date of follow-up.According to HPS gene test results,23 cases were divided into two groups: mutation group and non-mutation group.All data were analyzed statistically by a SPSS statistical software;comparison between two groups was conducted with the MANN-WHITNEY U test;the difference in the quantitative data between the groups was compared using Fisher test(sample<40);P<0.05 was considered statistically significant.Results:(1)Gene mutation related to HPS was detected in 56.3% cases.The mutations were mainly LYST(46.2%),UNC13D(38.5%),ITK(30.8%),STXBP2(15.2%),XIAP(7.7%),and no PRF1 gene mutation.(2)The gene mutations group includes 7 males and 6 female cases;the without gene mutations group includes 6 males and 4 female cases;there was no significant difference of gender between the two groups(P> 0.05).(3)Age of onset in the gene mutations group is 4.12±4.68 years;while the without gene mutations group is 5.82±4.16 years.There was no significant difference of gender between the two groups(P> 0.05). (4)There are at least two of the liver,spleen,lymph nodes were swelling in both two groups;neurological symptoms appeared in 2 cases(15.4%)of the gene mutations group;while the gene mutations group appeared in 4 cases(40%);the neurological index in the two groups is no statistically significant(P> 0.05);(5)There were 4 case(30.8%)of EB virus positive and 4 case(30.8%)of positive mycoplasma(30.8%)in the gene mutations group.There were 1 case(10%)of EB virus positive and 2 cases(20.0%)of mycoplasma positive in the without gene mutations group.Both are no significant difference between the two groups(P> 0.05).(6)In two groups,both the peripheral blood cells reduced and the low albuminemia were100%.The main test results were as follows: NK cell activity decreased(63.6%),SF increased>500ug/L(92.3%),ALT increased ≥40U/L(86.4%),LDH increased>215U/L(92.3%),TG increased>3.0mmol/L(53.8%),FIB<1.5g/L(76.9%),hemophagocytic showed in bone marrow smears(61.5%);while in the control group,NK cell activity decreased(80%),SF increased>500ug/L(80.0%),LDH increased>215U/L(80.0%),TG increased>3.0mmol/L(40.0%),FIB<1.5g/L(60.6%),hemophagocytic showed in bone marrow smears(40.0%).Except for hemoglobin(P=0.019),all dates of above have no significant difference(P>0.05).The above indexes were stratified by diagnostic value and then compared with each other,the indexes still have no statistically significant(P> 0.05).(7)7 cases survised in the gene mutations group group,6 cases are dead(46.2%);in the without gene mutations group,9 cases survised and 1 cases dead(10%).There was no significant difference between the two groups(P> 0.05).Conclusion:(1)The detection rate of primary hemophagocytic syndrome related mutations in children with HPS was higher(56.5%),Mostly heterozygous mutations of single or multiple genes,rare homozygous mutants.(2)The detection rate of primary hemophagocytic syndrome-related mutations in children with HPS was higher(56.5%),listed as LYST(46.2%),UNC13D(38.5%),ITK(30.8%),STXBP2(15.2%)and XIAP(7.7%);PRFI gene mutation is rare in this research. (3)Single/polygenic heterozygous mutation were detected in 13 HPS cases.Pathogenic meaning is not clear until now,but some children with cytotoxic granules dysfunction cannot be completely excluded the primary HPS,especially for the children with family genetic whose disease progression present more vigilant.(4)The age,sex,severity of disease,mycoplasma infection,EB virus infection and prognosis of children with HSP in our experiment were not related to the mutations related to primary hemophagocytic syndrome.