目的 研究Wiskott-Aldrich综合征（WAS）患儿的临床特征。方法 对13例WAS患儿的临床资料进行回顾性分析。结果 13例患儿均为男性，发病年龄3（1~48）月，确诊年龄24（1~60）月。13例患儿中仅3例为典型WAS，余10例均为X-连锁血小板减少症（XLT）。WAS评分为2（1~3）分，血小板计数为20.5（13~46）×109/L，平均血小板体积为8.1（6.7~12.1） fl。4例患儿行淋巴细胞亚群及免疫球蛋白检查，其中淋巴细胞占有核细胞百分比及CD3+T细胞占淋巴细胞百分比均减低者1例（25%）；CD3-CD56+NK细胞占淋巴细胞百分比减低者1例（25%）；IgG升高者1例（25%），IgM下降者2例（50%），IgA下降者1例（25%），4例患儿IgE均升高（100%）。13例患儿共发现13种14个基因突变，其中错义突变9例（65%），剪接突变2例（14%），无义突变2例（14%），移码突变1例（7%）。随访39（3~62）个月，13例患儿均存活。结论 Wiskott-Aldrich综合征发病年龄小，男性为主，主要临床特征为血小板减少伴血小板体积缩小，基因突变以错义突变为主。
Abstract
Objective To study the clinical features of Wiskott-Aldrich syndrome (WAS) in children. Methods A retrospective analysis was performed for the clinical data of 13 children with WAS. Results All 13 children were boys, with a median age of onset of 3 months (range 1-48 months) and a median age of 24 months (range 1-60 months) at the time of diagnosis. Of the 13 children, only 3 had typical WAS and the remaining 10 children had X-linked thrombocytopenia (XLT). The mean WAS score was 2 (range 1-3), the mean platelet count was 20.5×109/L[range (13-46)×109/L], and the mean platelet volume was 8.1 fl (range 6.7-12.1 fl). Lymphocyte subsets and immunoglobulins were measured for 4 children, among whom 1 (25%) had a reduction in both the percentage of CD3+T cells per lymphocyte and lymphocyte per nuclear cells, 1(25%) had a reduction in CD3-CD56+ NK cells. Among these 4 children, 1 (25%) had an increase in IgG, 2 (50%) had a reduction in IgM, 1 (25%) had a reduction in IgA, and 4 (100%) had an increase in IgE. A total of 14 gene mutations belonging to 13 types were found in 13 children, among which there were 9 missense mutations (65%), 2 splicing mutations (14%), 2 nonsense mutation (14%), and 1 frameshift mutation (7%). The median follow-up time was 39 months (range 3-62 months), and all 13 children survived. Conclusions Children with WAS often have a young age of onset, and most of them are boys. Major clinical features include thrombocytopenia with a reduction in platelet volume. Missense mutation is the main type of gene mutation.
关键词
Wiskott-Aldrich综合征 /
血小板减少 /
基因 /
临床特征 /
儿童
Key words
Wiskott-Aldrich syndrome /
Thrombocytopenia /
Gene /
Clinical feature /
Child
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参考文献
[1] Worth AJ, Thrasher AJ. Current and emerging treatment options for Wiskott-Aldrich syndrome[J]. Expert Rev Clin Immunol, 2015, 11(9):1015-1032.
[2] Aldrich RA, Steinberg AG, Campbell DC. Pedigree demonstrating a sex-linked recessive condition characterized by draining ears, eczematoid dermatitis and bloody diarrhea[J]. Pediatrics, 1954, 13(2):133-139.
[3] de Saint Basile G, Arveiler B, Fraser NJ, et al. Close linkage of hypervariable marker DXS255 to disease locus of Wiskott-Aldrich syndrome[J]. Lancet, 1989, 2(8675):1319-1321.
[4] Derry JM, Ochs HD, Francke U. Isolation of a novel gene mutated in Wiskott-Aldrich syndrome[J]. Cell, 1994, 78(4):635-644.
[5] Massaad MJ, Ramesh N, Geha RS. Wiskott-Aldrich syndrome:a comprehensive review[J]. Ann N Y Acad Sci, 2013, 1285:26-43.
[6] Zhu Q, Zhang M, Blaese RM, et al. The Wiskott-Aldrich syndrome and X-linked congenital thrombocytopenia are caused by mutations of the same gene[J]. Blood, 1995, 86(10):3797-3804.
[7] 肖慧勤, 张志勇, 蒋利萍, 等. Wiskott-Aldrich综合征10例临床特点与实验室诊断分析[J]. 免疫学杂志, 2010, 26(1):43-48.
[8] Zhu Q, Watanabe C, Liu T, et al. Wiskott-Aldrich syndrome/X-linked thrombocytopenia:WASP gene mutations, protein expression, and phenotype[J]. Blood, 1997, 90(7):2680-2689.
[9] Ochs HD. The Wiskott-Aldrich syndrome[J]. Isr Med Assoc J, 2002, 4(5):379-384.
[10] 赵惠君. Wiskott-Aldrich综合征诊断治疗进展[J]. 中华实用儿科临床杂志, 2016, 31(15):1129-1132.
[11] Jin Y, Mazza C, Christie JR, et al. Mutations of the Wiskott-Aldrich Syndrome Protein (WASP):hotspots, effect on transcription, and translation and phenotype/genotype correlation[J]. Blood, 2004, 104(13):4010-4019.
[12] Notarangelo LD, Mazza C, Giliani S, et al. Missense mutations of the WASP gene cause intermittent X-linked thrombocytopenia[J]. Blood, 2002, 99(6):2268-2269.
[13] 李文言, 刘大玮, 张璇, 等. Wiskott-Aldrich综合征132例临床特点及基因型分析[J]. 中华儿科杂志, 2015, 53(12):925-930.
[14] Blundell MP, Worth A, Bouma G, et al. The Wiskott-Aldrich syndrome:the actin cytoskeleton and immune cell function[J]. Dis Markers, 2010, 29(3-4):157-175.
[15] Sullivan KE, Mullen CA, Blaese RM, et al. A multiinstitutional survey of the Wiskott-Aldrich syndrome[J]. J Pediatr, 1994, 125(6 Pt 1):876-885.
[16] Worth AJ, Thrasher AJ. Current and emerging treatment options for Wiskott-Aldrich syndrome[J]. Expert Rev Clin Immunol, 2015, 11(9):1015-1032.
[17] Moratto D, Giliani S, Bonfim C, et al. Long-term outcome and lineage-specific chimerism in 194 patients with Wiskott-Aldrich syndrome treated by hematopoietic cell transplantation in the period 1980-2009:an international collaborative study[J]. Blood, 2011, 118(6):1675-1684.
[18] Gerrits AJ, Leven EA, Frelinger AL 3rd, et al. Effects of eltrombopag on platelet count and platelet activation in Wiskott-Aldrich syndrome/X-linked thrombocytopenia[J]. Blood, 2015, 126(11):1367-1378.
[19] Dupré L, Marangoni F, Scaramuzza S, et al. Efficacy of gene therapy for Wiskott-Aldrich syndrome using a WAS promoter/cDNA-containing lentiviral vector and nonlethal irradiation[J]. Hum Gene Ther, 2006, 17(3):303-313.
[20] Astrakhan A, Sather BD, Ryu BY, et al. Ubiquitous high-level gene expression in hematopoietic lineages provides effective lentiviral gene therapy of murine Wiskott-Aldrich syndrome[J]. Blood, 2012, 119(19):4395-4407.
[21] Boztug K, Schmidt M, Schwarzer A, et al. Stem-cell gene therapy for the Wiskott-Aldrich syndrome[J]. N Engl J Med, 2010, 363(20):1918-1927.
[22] Hacein-Bey Abina S, Gaspar HB, Blondeau J, et al. Outcomes following gene therapy in patients with severe Wiskott-Aldrich syndrome[J]. JAMA, 2015, 313(15):1550-1563.
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