Clinical features of Wiskott-Aldrich syndrome: an analysis of 13 cases
LIU Chao, CHEN Xiao-Yan, WU Wen-Qi, AN Wen-Bin, CHANG Li-Xian, LAN Yang, YI Mei-Hui, CAI Yu-Li, FENG Jing, ZHU Xiao-Fan
Department of Pediatric Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
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.
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.
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.
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.
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.
