| ObjectiveBy summarizing and analyzing the clinical manifestations,immunology and genetic characteristics of Wiskott-Aldrich syndrome(WAS)in children,the aim is to improve the diagnosis and treatment of this disease.MethodsClinical data,blood routine and immunology-related laboratory examination results of 6 children with WAS were collected from the First Affiliated Hospital of Guangxi Medical University and Xiamen Children’s Hospital of Fudan University from 2018 to 2020.The high-throughput second-generation sequencing technology WAS used to detect WAS mutated genotypes after Sanger first-generation sequencing verification.The expression of WASp in the peripheral blood mononuclear cells(PBMC)of 6 children and their mothers was detected by flow cytometry.Results1.Clinical data:All the 6 cases were male,aged from 3 months to 119months,with a median age of 16 months,and all of them were from southern China(Guangxi,Fujian and Jiangxi).Except for 1 case of Zhuang nationality,the other 5 cases were all Han nationality.The onset age of all the 6 children was in infancy,and most of them had a history of eczema.None of them had a similar history in their family.All the 6 children had a history of bleeding to varying degrees and repeated infection,among which 1 patient had Henoch Schonlein purpura nephritis,1 patient had inflammatory bowel disease,and 1patient had inflammatory bowel disease combined with autoimmune hemolytic anemia.The clinical phenotypic score of 1 child WAS 2,indicating X-linked thrombocytopenia(XLT),and the scores of 5 children were all greater than or equal to 3,indicating typical WAS.At present,2 cases were treated conservatively,1 case was waiting for transplantation,3 cases had received transplantation treatment,2 cases recovered well after transplantation,and 1case still had recurrent hemolysis after transplantation.2.Blood routine and immunology:The platelet count of 6 children at first diagnosis ranged from 4×10~9/L to 36×10~9/L,with an average of 24.6×10~9/L;Platelet volume(MPV)8fl-9.7fl,mean 8.8fl.There were 4 children with mild anemia,neutrophils of 6 children were all normal and 2 children with mild eosinophil elevation.Among the 6 cases,1 case(12.7%)had elevated Ig G,3cases(50%)had Ig M decrease and 3 cases(50%)had Ig A increase.Ig E levels were normal in all 4 children.T lymphocytes and CD8+decreased in 2 cases(40%),and CD4+decreased in 4 cases(80%).NK cells decreased in 1(25%)of the 4 children,and CD19+was normal.3.WASp expression level:The expression level of WASp in all the 6 cases was abnormal,and WASp was not expressed in the other 5 cases except 1 case(P5).The expression of WASp was normal in 1 of 6 mothers(P4 mother),except for the partial expression of WASp.4.Gene mutation:A total of 6 WAS mutant genotypes were found in 6WAS families in this study.There were 2 missense mutations(WAS Val75Met,WAS Phe74Ser),1 splice site mutation(WAS 559+5G>A),1 frame-shift mutation(WAS Pro414Serfs78),2 nonsense mutations(WAS Arg364Ter,WAS Gly243Ter).Two of the mutations were unreported.Except 1 case of neonatal mutation,the other 5 cases were all from the mother of the child.Conclusion1.The onset time of WAS children is early,and the earliest onset can be after birth,which is more common in male patients.2.Most of the patients in this case group had mild eczema,thrombocytopenia and different degrees of immunodeficiency,and the expression of WASp was reduced or even not expressed.3.A total of two unreported WAS mutations were found in this case group,namely WAS Pro414Serfs78 and WAS Gly243Ter,which further enriched the data related to WAS mutations.4.Children with unexplained bleeding,eczema or repeated infection in the neonatal period should be alert to the possibility of WAS,and screening and further identification of WAS gene should be carried out through WASP test as soon as possible. |
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