When WAS Gene Diagnosis Is Needed: Seeking Clues Through Comparison Between Patients With Wiskott-Aldrich Syndrome and Idiopathic Thrombocytopenic Purpura
Background: Wiskott-Aldrich syndrome (WAS) is a rare and severe X-linked disorder with variable clinical phenotypes correlating with the type of mutations in the WAS gene. The syndrome is difficult to differentiate from idiopathic thrombocytopenic purpura (ITP) before genetic diagnosis. We retrospec...
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Frontiers Media S.A.
2019-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.01549/full |
| _version_ | 1818419087956508672 |
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| author | Ying-Ying Jin Jing Wu Tong-Xin Chen Tong-Xin Chen Ji Chen |
| author_facet | Ying-Ying Jin Jing Wu Tong-Xin Chen Tong-Xin Chen Ji Chen |
| author_sort | Ying-Ying Jin |
| collection | DOAJ |
| description | Background: Wiskott-Aldrich syndrome (WAS) is a rare and severe X-linked disorder with variable clinical phenotypes correlating with the type of mutations in the WAS gene. The syndrome is difficult to differentiate from idiopathic thrombocytopenic purpura (ITP) before genetic diagnosis. We retrospectively reviewed patients suspected to have WAS who were referred to our hospital from 2004 to 2016 and compared the clinical features and laboratory examination of genetically confirmed WAS patients and of patients diagnosed with ITP in order to seek some clues to distinguish WAS and ITP before genetic diagnosis.Methods: Seventy-eight children suspected to have WAS from 78 unrelated families were enrolled in this study. The clinical data and laboratory examination of children were reviewed in the present study. The distribution of lymphocyte subsets from peripheral blood was examined by how cytometry. WASP mutations were identified by direct sequencing of PCR-amplified genomic DNA.Results: Forty-two patients were finally diagnosed with WAS genetically. The median onset age of these patients was 1 month (range: 1 day−10 months). The median diagnosis lag was 4.6 months (range: 0 months−9.42 years). Fifteen patients (35.71%) had positive family histories. More than half of the patients (n = 23, 54.76%) had diarrhea. Twenty-three (54.76%) had pneumonia, 7 with severe symptoms. Major bleeding events included skin spots or petechiae (n = 27, 64.29%), per-rectal bleeding (n = 21, 50.00%), epistaxis (n = 7, 16.67%) and intracranial bleeding (n = 2, 4.76%). Twenty-nine patients (69.05%) had eczema, and one patient had a drug allergy. Three patients had autoimmune diseases, among whom 2 had autoimmune hemolytic anemia and one had autoimmune hemolytic anemia and IgA nephropathy. A total of 42 mutations in WASP were identified, including 19 novel mutations. Eight patients received hematopoietic stem cell transplantation (HSCT) and all survived. Compared with the 30 patients diagnosed with ITP, the WAS patients had higher EOS counts and elevated IgE level, increased NK cell numbers but fewer CD8+T lymphocytes.Conclusion: The WAS gene diagnosis should be considered in all males with ITP-like features, especially for patients with a very early onset age, decreased MPV (<6.5 fl), higher EOS counts and elevated IgE level, increased NK cell number, diminished CD8+T lymphocyte count. |
| first_indexed | 2024-12-14T12:33:00Z |
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| id | doaj.art-8574676181724e3eb379026e508f44e6 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-14T12:33:00Z |
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| spelling | doaj.art-8574676181724e3eb379026e508f44e62022-12-21T23:01:07ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-07-011010.3389/fimmu.2019.01549449385When WAS Gene Diagnosis Is Needed: Seeking Clues Through Comparison Between Patients With Wiskott-Aldrich Syndrome and Idiopathic Thrombocytopenic PurpuraYing-Ying Jin0Jing Wu1Tong-Xin Chen2Tong-Xin Chen3Ji Chen4Department of Rheumatology/Immunology, Children's National Medical Center, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDivision of Immunology, Institute of Pediatric Translational Medicine, Children's National Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Rheumatology/Immunology, Children's National Medical Center, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDivision of Immunology, Institute of Pediatric Translational Medicine, Children's National Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Dermatology, Children's National Medical Center, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaBackground: Wiskott-Aldrich syndrome (WAS) is a rare and severe X-linked disorder with variable clinical phenotypes correlating with the type of mutations in the WAS gene. The syndrome is difficult to differentiate from idiopathic thrombocytopenic purpura (ITP) before genetic diagnosis. We retrospectively reviewed patients suspected to have WAS who were referred to our hospital from 2004 to 2016 and compared the clinical features and laboratory examination of genetically confirmed WAS patients and of patients diagnosed with ITP in order to seek some clues to distinguish WAS and ITP before genetic diagnosis.Methods: Seventy-eight children suspected to have WAS from 78 unrelated families were enrolled in this study. The clinical data and laboratory examination of children were reviewed in the present study. The distribution of lymphocyte subsets from peripheral blood was examined by how cytometry. WASP mutations were identified by direct sequencing of PCR-amplified genomic DNA.Results: Forty-two patients were finally diagnosed with WAS genetically. The median onset age of these patients was 1 month (range: 1 day−10 months). The median diagnosis lag was 4.6 months (range: 0 months−9.42 years). Fifteen patients (35.71%) had positive family histories. More than half of the patients (n = 23, 54.76%) had diarrhea. Twenty-three (54.76%) had pneumonia, 7 with severe symptoms. Major bleeding events included skin spots or petechiae (n = 27, 64.29%), per-rectal bleeding (n = 21, 50.00%), epistaxis (n = 7, 16.67%) and intracranial bleeding (n = 2, 4.76%). Twenty-nine patients (69.05%) had eczema, and one patient had a drug allergy. Three patients had autoimmune diseases, among whom 2 had autoimmune hemolytic anemia and one had autoimmune hemolytic anemia and IgA nephropathy. A total of 42 mutations in WASP were identified, including 19 novel mutations. Eight patients received hematopoietic stem cell transplantation (HSCT) and all survived. Compared with the 30 patients diagnosed with ITP, the WAS patients had higher EOS counts and elevated IgE level, increased NK cell numbers but fewer CD8+T lymphocytes.Conclusion: The WAS gene diagnosis should be considered in all males with ITP-like features, especially for patients with a very early onset age, decreased MPV (<6.5 fl), higher EOS counts and elevated IgE level, increased NK cell number, diminished CD8+T lymphocyte count.https://www.frontiersin.org/article/10.3389/fimmu.2019.01549/fullWiskott-Aldrich syndromeidiopathic thrombocytopenic purpuraprimary immunodeficiencygene mutationhematopoietic stem cell transplantation |
| spellingShingle | Ying-Ying Jin Jing Wu Tong-Xin Chen Tong-Xin Chen Ji Chen When WAS Gene Diagnosis Is Needed: Seeking Clues Through Comparison Between Patients With Wiskott-Aldrich Syndrome and Idiopathic Thrombocytopenic Purpura Frontiers in Immunology Wiskott-Aldrich syndrome idiopathic thrombocytopenic purpura primary immunodeficiency gene mutation hematopoietic stem cell transplantation |
| title | When WAS Gene Diagnosis Is Needed: Seeking Clues Through Comparison Between Patients With Wiskott-Aldrich Syndrome and Idiopathic Thrombocytopenic Purpura |
| title_full | When WAS Gene Diagnosis Is Needed: Seeking Clues Through Comparison Between Patients With Wiskott-Aldrich Syndrome and Idiopathic Thrombocytopenic Purpura |
| title_fullStr | When WAS Gene Diagnosis Is Needed: Seeking Clues Through Comparison Between Patients With Wiskott-Aldrich Syndrome and Idiopathic Thrombocytopenic Purpura |
| title_full_unstemmed | When WAS Gene Diagnosis Is Needed: Seeking Clues Through Comparison Between Patients With Wiskott-Aldrich Syndrome and Idiopathic Thrombocytopenic Purpura |
| title_short | When WAS Gene Diagnosis Is Needed: Seeking Clues Through Comparison Between Patients With Wiskott-Aldrich Syndrome and Idiopathic Thrombocytopenic Purpura |
| title_sort | when was gene diagnosis is needed seeking clues through comparison between patients with wiskott aldrich syndrome and idiopathic thrombocytopenic purpura |
| topic | Wiskott-Aldrich syndrome idiopathic thrombocytopenic purpura primary immunodeficiency gene mutation hematopoietic stem cell transplantation |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.01549/full |
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