title: [Clinical features and genotype analysis of 132 patients with Wiskott-Aldrich syndrome].
abstract: OBJECTIVE
  To investigate the clinical and immunological laboratory features, gene mutations, treatment and prognosis in children with Wiskott-Aldrich syndrome (WAS).
  
  
  METHODS
  The clinical, laboratory characteristics, treatment and prognosis of 132 children with WAS, who visited Children's Hospital of Chongqing Medical University from April 2000 to June 2015, were analyzed retrospectively.
  
  
  RESULTS
  All patients were male. The median age of disease onset was 15 days and the median age at diagnosis was 10 months. Of the 132 cases, 112 had classic WAS, 20 had X-linked thrombocytopenia (XLT). The median platelet count was 23×10(9)/L. All cases had the clinical characteristics of WAS including bleeding, eczema, and being susceptible to infection. The initial symptoms include hemorrhage (75.0%) and eczema (16.7%). Twenty-one cases had autoimmune diseases and one patient had leukemia. WAS protein (WASP) expression in 115 cases were measured by flow cytometry, 88 cases were negative, in 12 cases WASP decreased, in 5 cases it was normal, 10 cases had bimodal distribution. Eighty-one kinds of mutations were found in 122 families, including eight kinds of hot-spot mutations, which were 290 C> N / 291G> N (R86C / H / L), 665 C> T (R211X), 155 C> T (R41X), 168 C> T (T45 M), IVS1+ 1 g> t/ a, IVS6 + 5 g> a, IVS8 + 1 g> a and IVS8 + 1to + 6del gtga. Meantime, 29 kinds of novel mutations were found, which were 321T>C, 415C>A, 471C>T, 102-105delC, 521 del C, 1330 del A, IVS2-2 a>c, 168 C>A/1412 C> T, exon1-2 del/1412 C>T, and so on. The proportion of CD3(+) T cells (31.3%), helper T cells (37.3%) and cytotoxic T cells (38.6%) in the peripheral blood declined. The serum levels of IgG (51.1%), IgA (43.3%) and IgE (40.0%) increased, IgM (25.6%) decreased. Of the 132 cases, 72 remain survived, of whom 36 cases received hematopoietic stem cell transplantation (HSCT), 14 patients with classic WAS received intravenous immunoglobulin (IVIG) therapy. With regular IVIG therapy, the frequency of infections was reduced and the patients' symptoms were improved.
  
  
  CONCLUSIONS
  The clinical characteristics of Wiskott-Aldrich syndrome were early age of onset, microthrombocytopenia, eczema and recurrent infections. The proportion of T lymphocyte declined, the serum levels of IgG, IgA, and IgE increased, and level of IgM decreased in a part of patients. The detection of WAS gene mutation and WAS protein detection was the key diagnostic methods. Regular IVIG can gain more time for children who will receive HSCT and improve their quality of life.
authors.affiliation: Department of Nephrology and Immunology, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing 400014, China.
authors.forename: Wenyan
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Nephrology and Immunology, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing 400014, China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Nephrology and Immunology, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing 400014, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Nephrology and Immunology, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing 400014, China; Email: dingyuan1981444@aliyun.com.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Nephrology and Immunology, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing 400014, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhao
mesh_terms: D040181:Genetic Diseases, X-Linked / Q000235:genetics; D005838:Genotype; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D010976:Platelet Count; D012189:Retrospective Studies; D013921:Thrombocytopenia / Q000235:genetics; D014923:Wiskott-Aldrich Syndrome / Q000235:genetics*; D051316:Wiskott-Aldrich Syndrome Protein / Q000235:genetics
chemical_list: D016756:Immunoglobulins, Intravenous; C495767:WAS protein, human; D051316:Wiskott-Aldrich Syndrome Protein