Wiskott–Aldrich syndrome that was initially diagnosed as immune thrombocytopenic purpura secondary to a cytomegalovirus infection

Kaneko, Ryota; Yamamoto, Shohei; Okamoto, Nobuhiko; Akiyama, Kosuke; Matsuno, Ryosuke; Toyama, Daisuke; Hoshino, Akihiro; Imai, Kohsuke; Isoyama, Keiichi

doi:10.1177/2050313x17753788

Cited by 8 publications

(9 citation statements)

References 4 publications

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“…However, WAS is sometimes difficult to differentiate from other thrombocytopenic disorders and is often initially diagnosed as idiopathic thrombocytopenic purpura (ITP), which can lead to inappropriate treatment and delays to life-saving definitive therapy (11–13). WAS is traditionally differentiated from ITP by the small size of WAS platelets (14).…”

Section: Introductionmentioning

confidence: 99%

When WAS Gene Diagnosis Is Needed: Seeking Clues Through Comparison Between Patients With Wiskott-Aldrich Syndrome and Idiopathic Thrombocytopenic Purpura

Jin

Chen

et al. 2019

Front. Immunol.

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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.

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Section: Introductionmentioning

confidence: 99%

When WAS Gene Diagnosis Is Needed: Seeking Clues Through Comparison Between Patients With Wiskott-Aldrich Syndrome and Idiopathic Thrombocytopenic Purpura

Jin

Chen

et al. 2019

Front. Immunol.

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“…Sino-pulmonary infections were the commonest infection in our cohort. Viral infections from Varicella-zoster virus (VZV), Herpes simplex virus (HSV), EBV, CMV, and Human papillomavirus (HPV) can be extremely severe CMV infection in WAS needs particular attention and often poses a diagnostic dilemma (38,(41)(42)(43). Thrombocytopenia may be erroneously ascribed to CMV infection and underlying diagnosis of WAS is often missed or delayed (41,42).…”

Section: Discussionmentioning

confidence: 99%

Wiskott Aldrich Syndrome: A Multi-Institutional Experience From India

et al. 2021

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BackgroundWiskott Aldrich syndrome (WAS) is characterized by bleeding manifestations, recurrent infections, eczema, autoimmunity, and malignancy. Over the last decade, improved awareness and better in-house diagnostic facilities at several centers in India has resulted in increased recognition of WAS. This study reports collated data across major primary immunodeficiency diseases (PID) centers in India that are involved in care of children with WAS and highlights the varied clinical presentations, genetic profile, and outcomes of patients in India.MethodsRequest to share data was sent to multiple centers in India that are involved in care and management of patients with PID. Six centers provided requisite data that were compiled and analyzed.ResultsIn this multi-institutional cohort, clinical details of 108 patients who had a provisional diagnosis of WAS were received. Of these, 95 patients with ‘definite WAS’ were included Fourteen patients were classified as XLT and 81 patients as WAS. Median age at onset of symptoms of patients was 3 months (IQR 1.6, 6.0 months) and median age at diagnosis was 12 months (IQR 6,48 months). Clinical profile included bleeding episodes (92.6%), infections (84.2%), eczema (78.9%), various autoimmune manifestations (40%), and malignancy (2.1%). DNA analysis revealed 47 variants in 67 cases. Nonsense and missense variants were the most common (28.4% each), followed by small deletions (19.4%), and splice site defects (16.4%). We also report 24 novel variants, most of these being frameshift and nonsense mutations resulting in premature termination of protein synthesis. Prophylactic intravenous immunoglobulin (IVIg) was initiated in 52 patients (54.7%). Hematopoietic stem cell transplantation (HSCT) was carried out in 25 patients (26.3%). Of those transplanted, disease-free survival was seen in 15 patients (60%). Transplant related mortality was 36%. Outcome details were available for 89 patients. Of these, 37% had died till the time of this analysis. Median duration of follow-up was 36 months (range 2 weeks- 12 years; IQR 16.2 months- 70 months).ConclusionsWe report the first nationwide cohort of patients with WAS from India. Bleeding episodes and infections are common manifestations. Mortality continues to be high as curative therapy is not accessible to most of our patients.

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“…A WAS gene analysis was conducted and revealed a positive result. WAS, in general, was reported as difficult to differentiate from ITP [ 50 , 51 , 52 , 53 ]. It could be due to the loss of functional mutations in the WAS gene located in the X chromosome (position Xp11.22-p11.23), and the pathogenic mutations that occur within the exons and introns [ 54 , 55 ].…”

Section: Immune Thrombocytopenia and Autoimmune Diseasesmentioning

confidence: 99%

A Review on Secondary Immune Thrombocytopenia in Malaysia

et al. 2021

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Immune thrombocytopenia (ITP) is an acquired autoimmune disease that occurs in adults and children. In Malaysia, the clinical practice guideline (CPG) for the management of ITP was issued in 2006, which focused almost exclusively on primary ITP (pITP), and only a few secondary ITP (sITP) forms were addressed. All published (twenty-three) sITP articles among children and adults in Malaysia, identified on the academic databases were retrieved. The articles were published between 1981 and 2019, at a rate of 0.62 publications per year. The publications were considered low and mainly focused on rare presentation and followed-up of secondary diseases. This review revealed that sITP in Malaysia is commonly associated with autoimmune diseases (Evan’s syndrome, SLE and WAS), malignancy (Kaposi’s sarcoma and breast cancer) and infection (dengue haemorrhagic fever, Helicobacter pylori and hepatitis C virus). The relationship between ITP and autoimmune diseases, malignancy and infections raise the question concerning the mechanism involved in these associations. Further studies should be conducted to bridge the current knowledge gap, and the further information is required to update the existing CPG of management of ITP in Malaysia.

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Wiskott–Aldrich syndrome that was initially diagnosed as immune thrombocytopenic purpura secondary to a cytomegalovirus infection

Cited by 8 publications

References 4 publications

When WAS Gene Diagnosis Is Needed: Seeking Clues Through Comparison Between Patients With Wiskott-Aldrich Syndrome and Idiopathic Thrombocytopenic Purpura

When WAS Gene Diagnosis Is Needed: Seeking Clues Through Comparison Between Patients With Wiskott-Aldrich Syndrome and Idiopathic Thrombocytopenic Purpura

Wiskott Aldrich Syndrome: A Multi-Institutional Experience From India

A Review on Secondary Immune Thrombocytopenia in Malaysia

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