Wiskott-Aldrich综合征32例病例系列报告OA

Background Wiskott-Aldrich syndrome(WAS)is a rare X-linked recessive disorder caused by mutations in the WAS gene.Currently,systematic reports on this condition remain limited in both domestic and international literature.Objective To investigate the clinical manifestations,genetic characteristics,treatment,and prognosis of Chinese children with WAS.Design Case series report.Methods A retrospective analysis was conducted on children with WAS admitted to Clinical Immunology and Allergy Department,Children's Hospital of Fudan University,from January 2015 to December 2024.Their clinical characteristics were summarized.Main Outcome Measures Laboratory findings,genetic features,and follow-up outcomes of treatments.Results(1)A total of 32 patients were enrolled,all of whom were male.The median age at onset was 9 days(range:0 days to 3 years),and the median age at diagnosis was 3 months and 26 days(range:20 days to 14 years).Among them,21 cases were classified as classic WAS,5 as X-linked thrombocytopenia(XLT),4 as intermittent XLT(IXLT),and 2 as X-linked neutropenia(XLN).(2)The most common initial symptom was bleeding,observed in 59.4%(19 cases),followed by jaundice in 18.8%(6 cases),eczema in 15.6%(5 cases),and infection in 15.6%(5 cases).During the disease course,50.0%(16 cases)exhibited varying degrees of bleeding manifestations,including intracranial hemorrhage in 2 cases.Autoimmune thyroiditis developed in 2 patients,and inflammatory bowel disease in 1 patient.(3)Genetic testing of the 32 patients revealed WAS gene missense mutations in 16 cases,deletion-frameshift mutations in 7 cases,splicing mutations in 6 cases,nonsense mutations in 2 cases,and a duplication mutation in 1 case.All mutations were pathogenic,among which 6 were previously unreported:c.137C>T,c.727G>T,c.1158delT,c.604delA,c.442dupA,and c.8G>A.WAS protein expression was decreased or absent in 17 cases and normal in 3 cases.(4)Immunological evaluation showed abnormalities in peripheral blood lymphocyte subsets in 84.4%of patients and abnormal immunoglobulin levels in 29.0%.Reductions were observed in total T lymphocytes(17 cases),total B lymphocytes(19 cases),NK cells(11 cases),IgG(3 cases),IgA(3 cases),and IgM(9 cases).(5)Neurological assessment revealed abnormalities in 43.8%of patients,including developmental delay in 6 cases and intellectual disability in 3 cases.(6)Follow-up results showed that 53.1%(17 cases)underwent hematopoietic stem cell transplantation(HSCT),of whom 13 achieved favorable outcomes and 4 died.Among the 6 patients who did not undergo transplantation,none showed significant symptom improvement,all had developmental delay,and 2 had intellectual disability.Conclusion Wiskott-Aldrich syndrome is characterized by early onset,thrombocytopenia,eczema,recurrent infections,and possible neurological involvement.Genetic analysis combined with WAS protein detection is crucial for early diagnosis.Early HSCT should be cairied out as soon as possible for those conform to the transplantation criteria.