Wiskott-Aldrich syndrome: a study of 577 patients defines the genotype as a biomarker for disease severity and survival.

ABSTRACT: Wiskott-Aldrich syndrome (WAS) is a multifaceted monogenic disorder with a broad disease spectrum and variable disease severity and a variety of treatment options including allogeneic hematopoietic stem cell transplantation (HSCT) and gene therapy (GT). No reliable biomarker exists to predict disease course and outcome for individual patients. A total of 577 patients with a WAS variant from 26 countries and a median follow-up of 8.9 years (range, 0.3-71.1), totaling 6118 patient-years, were included in this international retrospective study. Overall survival (OS) of the cohort (censored at HSCT or GT) was 82% (95% confidence interval, 78-87) at age 15 years and 70% (61-80) at 30 years. The type of variant was predictive of outcome: patients with a missense variant in exons 1 or 2 or with the intronic hot spot variant c.559+5G>A (class I variants) had a 15-year OS of 93% (89-98) and a 30-year OS of 91% (86-97), compared with 71% (62-81) and 48% (34-68) in patients with any other variant (class II; P < .0001). The cumulative incidence rates of disease-related complications such as severe bleeding (P = .007), life-threatening infection (P < .0001), and autoimmunity (P = .004) occurred significantly later in patients with a class I variant. The cumulative incidence of malignancy (P = .6) was not different between classes I and II. It confirms the spectrum of disease severity and quantifies the risk for specific disease-related complications. The class of the variant is a biomarker to predict the outcome for patients with WAS.

Trasplante de médula ósea haploidéntico en un paciente pediátrico con síndrome de Wiskott-Aldrich. A propósito de un caso / Haploidentical bone marrow transplantation in a pediatric patient with Wiskott-Aldrich syndrome. A case report

El síndrome de Wiskott-Aldrich es un error innato de la inmunidad de herencia ligada al cromosoma X, producido por variantes en el gen que codifica la proteína del síndrome de Wiskott-Aldrich (WASp). Reportamos el caso clínico de un paciente de 18 meses con diagnóstico de Wiskott-Aldrich que no presentaba donante antígeno leucocitario humano (HLA) idéntico y recibió un trasplante de células progenitoras hematopoyéticas (TCPH) con donante familiar haploidéntico. La profilaxis para enfermedad de injerto contra huésped incluyó ciclofosfamida (PT-Cy). El quimerismo del día +30 fue 100 % del donante y la evaluación postrasplante de la expresión de la proteína WAS fue normal. Actualmente, a 32 meses del trasplante, presenta reconstitución hematológica e inmunológica y quimerismo completo sin evidencia de enfermedad injerto contra huésped. El TCPH haploidéntico con PT-Cy se mostró factible y seguro en este caso de síndrome de WiskottAldrich en el que no se disponía de un donante HLA idéntico.

Wiskott-Aldrich syndrome (WAS) is an X-linked genetic disorder caused by mutations in the gene that encodes the Wiskott-Aldrich syndrome protein (WASp). Here, we report the clinical case of an 18-month-old boy diagnosed with Wiskott-Aldrich syndrome, who did not have an HLA-matched related or unrelated donor and was treated successfully with a hematopoietic stem cell transplant (HSCT) from a haploidentical family donor. Graft-versus-host disease (GvHD) prophylaxis included post-transplant cyclophosphamide (PT-Cy). At day +30, the peripheral blood-nucleated cell chimerism was 100% and the WAS protein had a normal expression. Currently, at month 32 post-transplant, the patient has hematological and immune reconstitution and complete donor chimerism without evidence of GvHD. HSCT with PT-Cy was a feasible and safe option for this patient with WAS, in which an HLA matched donor was not available.

Haploidentical bone marrow transplantation in a pediatric patient with Wiskott-Aldrich syndrome. A case report. / Trasplante de médula ósea haploidéntico en un paciente pediátrico con síndrome de Wiskott-Aldrich. A propósito de un caso.

Wiskott-Aldrich syndrome (WAS) is an X-linked genetic disorder caused by mutations in the gene that encodes the Wiskott-Aldrich syndrome protein (WASp). Here, we report the clinical case of an 18-month-old boy diagnosed with Wiskott-Aldrich syndrome, who did not have an HLA-matched related or unrelated donor and was treated successfully with a hematopoietic stem cell transplant (HSCT) from a haploidentical family donor. Graft-versus-host disease (GvHD) prophylaxis included post-transplant cyclophosphamide (PT-Cy). At day +30, the peripheral blood-nucleated cell chimerism was 100% and the WAS protein had a normal expression. Currently, at month 32 post-transplant, the patient has hematological and immune reconstitution and complete donor chimerism without evidence of GvHD. HSCT with PT-Cy was a feasible and safe option for this patient with WAS, in which an HLA matched donor was not available.

El síndrome de Wiskott-Aldrich es un error innato de la inmunidad de herencia ligada al cromosoma X, producido por variantes en el gen que codifica la proteína del síndrome de Wiskott-Aldrich (WASp). Reportamos el caso clínico de un paciente de 18 meses con diagnóstico de Wiskott-Aldrich que no presentaba donante antígeno leucocitario humano (HLA) idéntico y recibió un trasplante de células progenitoras hematopoyéticas (TCPH) con donante familiar haploidéntico. La profilaxis para enfermedad de injerto contra huésped incluyó ciclofosfamida (PT-Cy). El quimerismo del día +30 fue 100 % del donante y la evaluación postrasplante de la expresión de la proteína WAS fue normal. Actualmente, a 32 meses del trasplante, presenta reconstitución hematológica e inmunológica y quimerismo completo sin evidencia de enfermedad injerto contra huésped. El TCPH haploidéntico con PT-Cy se mostró factible y seguro en este caso de síndrome de WiskottAldrich en el que no se disponía de un donante HLA idéntico.

Rare solid tumors in a patient with Wiskott-Aldrich syndrome after hematopoietic stem cell transplantation: case report and review of literature.

Background and aims: Wiskott-Aldrich syndrome (WAS) is an X-linked recessive primary immunodeficiency disorder characterized by severe eczema, recurrent infections, and micro-thrombocytopenia. Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative therapeutic option for patients with classic form. The risk of developing post-transplant tumors appears to be higher in patients with WAS than in other inborn errors of immunity (IEIs), but the actual incidence is not well defined, due to the scarcity of published data. Methods: Herein, we describe a 10-year-old patient diagnosed with WAS, treated with HSCT in the first year of life, who subsequently developed two rare solid tumors, kaposiform hemangioendothelioma and desmoid tumor. A review of the literature on post-HSCT tumors in WAS patients has been performed. Results: The patient received diagnosis of classic WAS at the age of 2 months (Zhu score = 3), confirmed by WAS gene sequencing, which detected the nonsense hemizygous c.37C>T (Arg13X) mutation. At 9 months, patient underwent HSCT from a matched unrelated donor with an adequate immune reconstitution, characterized by normal lymphocyte subpopulations and mitogen proliferation tests. Platelet count significantly increased, even though platelet count never reached reference values. A mixed chimerism was also detected, with a residual WASP- population on monocytes (27.3%). The patient developed a kaposiform hemangioendothelioma at the age of 5. A second abdominal tumor was identified, histologically classified as a desmoid tumor when he reached the age of 10 years. Both hematopoietic and solid tumors were identified in long-term WAS survivors after HSCT. Conclusion: Here, we describe the case of a patient with WAS who developed two rare solid tumors after HSCT. An active surveillance program for the risk of tumors is necessary in the long-term follow-up of post-HSCT WAS patients.

[Wiskott-Aldrich syndrome with platelets of normal size and c.295C>T mutation of the WAS gene. Case report]. / Síndrome de Wiskott-Aldrich con plaquetas de tamaño normal y mutación c.295C>T en el gen WAS. Informe de caso.

BACKGROUND: Wiskott-Aldrich syndrome is an Inborn Error of Immunity characterized by thrombocytopenia, small platelets, severe eczema, recurrent infections, tendency to autoimmune diseases and neoplasms. The diagnosis of the syndrome can be difficult, especially when platelets are of normal size. CASE REPORT: A three-year-old male patient was referred to a specialized sector of university hospital for presenting acute otitis media that progressed to sepsis by Haemophilus influenzae. At one month of age, he had been diagnosed with autoimmune thrombocytopenia, and splenectomy was performed at two years of age. During follow-up, three hospitalizations were necessary: an infection by Streptococcus pneumoniae, which progressed to sepsis; one due to exacerbation of eczema, isolating S. epidermidis; another due to fever of undetermined origin. The tests showed normal number of platelets after splenectomy, platelets always with normal size. At age four, tests were performed: IgE 3128 Ku/L; IgA, IgG, and normal anti-polysaccharide antibodies; decreased IgM; decrease CD19, TCD4, naïve T and B; increased TCD8; normal NK. A diagnostic hypothesis of "probable" WAS was made. Genetic research has identified the c.295C>T mutation in the WAS gene. CONCLUSIONS: The case reported expressed a new mutation in the SWA gene, characterized by clinical manifestations of the mild phenotype of Wiskott-Aldrich syndrome, with thrombocytopenia, platelets of normal size, and X-linked inheritance. It is important to establish the early diagnosis and treatment to offer a better quality of life in these patients.

ANTECEDENTES: El síndrome de Wiskott-Aldrich es un error innato de la inmunidad, distinguido por trombocitopenia, plaquetas pequeñas, eccema severo, infecciones recurrentes, y susceptibilidad a enfermedades autoinmunes y neoplasias. El diagnóstico es difícil de establecer, especialmente cuando las plaquetas son de tamaño normal. REPORTE DE CASO: Paciente masculino de 3 años, enviado al Hospital Universitario da Santa Casa de São Paulo, Brasil, por otitis media aguda, con evolución a sepsis por Haemophilus influenzae. Al mes de edad fue diagnosticado con trombocitopenia autoinmune, y a los 2 años se llevó a cabo explenectomía. Durante el seguimiento requirió tres hospitalizaciones: una por infección por Streptococcus pneumoniae, que evolucionó a sepsis; otra por exacerbación de eccema, aislándose S. epidermidis, y la última por fiebre de origen indeterminado. Las pruebas de laboratorio informaron: concentración de plaquetas dentro de los valores de referencia después de la esplenectomía, y de tamaño normal. A los 4 años se efectuaron nuevas pruebas, que reportaron: IgE 3128 kU/L; IgA, IgG y anticuerpos anti-polisacáridos normales; disminución de IgM y de CD19, TCD4, T y B vírgenes; aumento de TCD8; NK normales. Se sospechó el diagnóstico de síndrome de Wiskott-Aldrich. Mediante estudios de genética se identificó la mutación c.295C>T en el gen WAS. CONCLUSIONES: El caso aquí expuesto expresó una nueva mutación en el gen SWA, caracterizado por manifestaciones clínicas de fenotipo leve del síndrome de Wiskott-Aldrich, con trombocitopenia, plaquetas de tamaño normal y herencia ligada al cromosoma X. Es importante establecer el diagnóstico y tratamiento oportunos para ofrecer una mejor calidad de vida en estos pacientes.

CMV Retinitis in Wiskott Aldrich Syndrome.

PURPOSE: Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disease whose optimal curative treatment is hematopoietic stem cell transplantation (HSCT). Patients with WAS may suffer from cytomegalovirus retinitis (CMVR) which can cause vision loss. This study is to report the progression and prognosis of patients with WAS and CMVR. METHODS: A retrospective case series of ten patients with WAS and CMVR before and after HSCT who were referred to the Ophthalmology Department of Xinhua Hospital from June 2018 to February 2021. Progression and prognosis were recorded. RESULTS: Five patients were diagnosed with CMVR before receiving HSCT at a median age of 10.5 months (range: 4-23 months). Eight patients developed CMVR post-transplantation with a median interval from HSCT of 3.5 months (range: 1-9 months). CONCLUSION: Regular fundus examinations and prompt treatments in patients with WAS are therefore crucial before they receiving HSCT or approximately 3.5 months after HSCT until complete reconstitution of immune function.

Confirmed diagnosis of classic Wiskott-Aldrich syndrome in East Africa: a case report.

INTRODUCTION: Wiskott-Aldrich syndrome is a rare X-linked primary immunodeficiency that mostly presents with a classic triad of eczema, microthrombocytopenia, recurrent infections, and increased risk of autoimmunity/malignancies. CASE PRESENTATION: We present an 8-month-old African male, born from nonconsanguineous parents and who presented with a history of eczematous skin rash since day 9 of life, with recurrent sinus infections, otitis media, and skin abscesses. An elder male sibling who had similar symptoms passed away during infancy. Investigations were consistent with microthrombocytopenia and significantly raised immunoglobulin E, while immunoglobulin A and immunoglobulin G were moderately elevated with normal immunoglobulin M. Genetic testing revealed the patient to be hemizygous for a pathogenic Wiskott-Aldrich syndrome gene variant (NM_000377.2:c.403C>T). He was managed conservatively with supportive treatment until he died a year later. CONCLUSION: Despite Wiskott-Aldrich syndrome being a rare disease, it should be considered as a differential in any male child who presents with microthrombocytopenia and recurrent infections, especially in low-resource settings where genetic testing is not routinely available.

Diagnosis and clinical management of Wiskott-Aldrich syndrome: current and emerging techniques.

INTRODUCTION: Wiskott-Aldrich syndrome (WAS) serves as the prototype of how variants in a gene, which encodes a protein central to actin cytoskeletal homeostasis can manifest clinically in a variety of ways including infection, atopy, autoimmunity, inflammation, bleeding, neutropenia, non-malignant lymphoproliferation, and malignancy. Despite the discovery of the WAS gene almost 30 years ago, our understanding of the pathophysiological mechanisms underlying WAS continues to unfold. AREAS COVERED: This review will provide an overview of the approach to the diagnosis of WAS as well as the management of its associated complications. Advances in the use of allogeneic hematopoietic stem cell transplantation (HSCT) and gene therapy as well as the associated challenges unique to WAS will be discussed. EXPERT OPINION: Basic research, combined with clinical research focusing on longitudinal analysis of WAS patients, will help clarify determinants that influence WAS pathogenesis as well as clinical complications and outcomes. Advances in curative approaches including the use of alternative donor HSCT for WAS continue to evolve. Gene therapy employing safer and more effective protocols ensuring full correction of WAS will provide life-saving benefit to WAS patients who are unable to undergo HSCT.

An Autopsy Case of Wiskott-Aldrich Syndrome Revealing "FDC-Only Lymphoid Follicles" in Lymphoid Tissue: A Morphologic Correlate of Defective Immune Synapse.

Wiskott-Aldrich Syndrome (WAS) is an inherited disorder characterized by the classical triad of eczema, micro-thrombocytopenia, and immune deficiency. This disease affects the hematopoietic cells to a variable extent. The spectrum of clinical and laboratory data for WAS has been well described in the literature though there is a paucity of its histopathologic and immunohistochemical correlates. The current case describes the autopsy findings of this rare entity in an 8-year old male child with specific recognition of altered histology noticed in the lymphoreticular tissues. The predominant morphological finding in lymphoid tissue was atretic hyalinized germinal centers labeled as "the follicular dendritic cell (FDC)-only lymphoid follicles." Immunohistochemistry revealed a reduction in germinal-center B-cells, T-follicular helper cells, attenuated mantle zone, FDC proliferation, and paracortical plasmacytosis. This case highlights the crippled immune cell population in WAS, ultimately leading to the morphology of atretic follicles rich in FDCs.

Acquired Thrombotic Thrombocytopenic Purpura in a 5-Year-old Child With Wiskott-Aldrich Syndrome.

Thrombocytopenia is often seen as a laboratory finding during childhood. A supposed idiopathic thrombocytopenic purpura patient who was later diagnosed as Wiskott-Aldrich syndrome (WAS) and developed acquired thrombotic thrombocytopenic purpura (aTTP). Although autoimmune manifestations in WAS described, aTTP was reported just once. Five-year-old-boy was initially brought with cough, bloody stool (diarrhea), oral mucosal bleeding at 12th months of age. Following diagnosed with idiopathic thrombocytopenic purpura and receiving intravenous immunoglobulin, platelet count raised from 20,000 to 50,000/µL. One year after WAS diagnosis by mutation analysis, he presented with complaints of resistant fever, epistaxis, and melena. Hemoglobin decreased from 10 to 5.9 g/dL. Schistocytes in peripheral blood smear and high anti-ADAMTS-13 antibody level indicated development of aTTP.

Clinical, Laboratory Features and Clinical Courses of Patients with Wiskott Aldrich Syndrome and X-linked Thrombocytopenia-A single center study.

OBJECTIVE: Wiskott Aldrich Syndrome is an X-linked primary immunodeficiency disorder characterized by microthrombocytopenia, severe immunodeficiency, and eczema. To define clinical-laboratory features, genetic defects (known/novel) of 23 patients of Wiskott Aldrich Syndrome/X-linked Thrombocytopenia (WAS/XLT) cohort, establish relationships between molecular defects and clinical features if present, evaluate patients who underwent hematopoietic stem cell transplantation (HSCT) and did not. METHODS: Qualitative analysis from patients' hospital files and Sanger sequencing for molecular diagnosis was performed. Twenty-two WAS patients and one XLT patient were included in the study. RESULTS: The median age of diagnosis was 15 months (2.5-172 months). The most common symptom was otitis media and all patients had microthrombocytopenia. Autoimmune findings were detected in 34.7% (8 patients) of the patients; three patients (13%) had positive anti-nuclear antibody (ANA), three patients (13%) hemolytic anemia, one patient autoimmune neutropenia, two patients vasculitis, and one patient demyelinating polyneuropathy. Nine of the 23 (39,1%) patients had HSCT with nearly 90% success. We identified 13 different mutations in our cohort; seven were novel. CONCLUSIONS: HSCT is the only curative treatment for WAS. The study confirms that early diagnosis is very important for the success of therapy, so we must increase awareness in society and physicians to keep an eye out for clues. Our study cohort and follow-up period are not sufficient to establish phenotype-genotype correlation, so a larger cohort from various centers with longer follow-up will be more decisive.

Report of clinical presentations and two novel mutations in patients with Wiskott-Aldrich syndrome/X-linked Thrombocytopenia.

Wiskott-Aldrich syndrome (WAS)/X-linked thrombocytopenia (XLT) is a rare X-linked disease characterized by thrombocytopenia, eczema, and recurrent infection. In addition, WAS/XLT increases incidence of autoimmune diseases and malignancies. We reported 7 male patients, 2 with WAS and 5 with XLT, from 6 different families. Two novel mutations, p.Gly387GlufsTer58 and p.Ala134Asp, were identified in patients with WAS. Both patients had severe clinical phenotypes compatible with classic WAS and developed lethal outcomes with intracranial hemorrhage. Other than that, one patient with XLT developed pineoblastoma.

Sinonasal diffuse large B-cell lymphoma in a patient with Wiskott-Aldrich syndrome: A case report and literature review.

Wiskott-Aldrich syndrome (WAS) is a rare primary immunodeficiency disease with a predisposition towards autoimmunity and lymphoproliferative diseases. Non-Hodgkin lymphoma (NHL) is reported to be the predominant form of malignant tumor in WAS sufferers. Diffuse large B-cell lymphoma (DLBCL) is one of the most common types of NHL while it is uncommon to occur in paranasal sinuses and especially when associated with WAS. In this article, we report a unique case of WAS associated with DLBCL in paranasal sinuses and review the major publications of WAS-related lymphomas that occurred in the head and neck area. This study extends the available therapies for WAS-related lymphomas and emphasizes the significance of recognition for sinonasal lymphomas in WAS patients presenting with sinusitis.

Wiskott Aldrich Syndrome: A Multi-Institutional Experience From India.

Background: Wiskott 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. Methods: Request 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. Results: In 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). Conclusions: We 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.

Clinical and genetic analysis of 2 rare cases of Wiskott-Aldrich syndrome from Chinese minorities: Two case reports.

RATIONALE: Wiskott-Aldrich syndrome (WAS) is a rare X-linked recessive disease characterized by thrombocytopenia, small platelets, eczema, immunodeficiency, and an increased risk of autoimmunity and malignancies. X-linked thrombocytopenia (XLT), the milder phenotype of WAS, is always limited to thrombocytopenia with absent or slight infections and eczema. Here, we illustrated the clinical and molecular characteristics of 2 unrelated patients with WAS from Chinese minorities. PATIENT CONCERNS: Patient 1, a 13-day-old male newborn of the Chinese Lahu minority, showed a classic WAS phenotype, including thrombocytopenia, small platelets, buttock eczema, and recurrent infections. Patient 2, an 8-year-and 8-month-old boy of the Chinese Zhuang minority, presented an XLT phenotype without eczema and repeated infections. DIAGNOSIS: Next-generation sequencing was performed to investigate the genetic variations. Flow cytometry was used to quantify the expression of WAS protein and analyze the lymphocyte subsets. A novel frameshift WAS mutation (c.927delC, p.Q310Rfs∗135) and a known nonsense WAS mutation (c.1090C>T, p.R364X) were identified in Patient 1 and Patient 2, respectively. Both patients were confirmed to have WAS protein deficiency, which was more severe in Patient 1. Meanwhile, the analysis of lymphocyte subsets revealed an abnormality in Patient 1, but not in Patient 2. Combined with the above clinical data and genetic characteristics, Patient 1 and Patient 2 were diagnosed as classic WAS and XLT, respectively. In addition, many miliary nodules were accidentally found in abdominal cavity of Patient 2 during appendectomy. Subsequently, Patient 2 was confirmed with pulmonary and abdominal tuberculosis through further laboratory and imaging examinations. To our knowledge, there have been only a few reports about WAS/XLT with tuberculosis. INTERVENTIONS: Both patients received anti-infection therapy, platelet transfusions, and intravenous immunoglobulins. Moreover, Patient 2 also received antituberculosis treatment with ethambutol and amoxicillin-clavulanate. OUTCOMES: The clinical symptoms and hematological parameters of these 2 patients were significantly improved. Regrettably, both patients discontinued the treatment for financial reasons. LESSONS: Our report expands the pathogenic mutation spectrum of WAS gene and emphasizes the importance of molecular genetic testing in diagnosing WAS. Furthermore, researching and reporting rare cases of WAS from different populations will facilitate diagnosis and treatment of this disease.

A Homozygous Mutation in 5' Untranslated Region of TNFRSF11A Leading to Molecular Diagnosis of Osteopetrosis Coinheritance With Wiskott-Aldrich Syndrome.

Wiskott-Aldrich syndrome (WAS) and osteopetrosis are 2 different, rare hereditary diseases. Here we report clinical and molecular genetics investigations on an infant patient with persistent thrombocytopenia and prolonged fever. He was clinical diagnosed as osteopetrosis according to clinical presentation, radiologic skeletal features, and bone biopsy results. Gene sequencing demonstrated a de novo homozygous mutation in 5'-untranslated region of TNFRSF11A, c.-45A>G, which is relating to osteopetrosis. Meanwhile, a hemizygous transition mutation in WAS gene, c.400G>A diagnosed the infant with WAS. This is the first clinical report for the diagnosis of osteopetrosis coinheritance with WAS in a single patient.

A Case With Wiskott-Aldrich Syndrome and Ascending Aorta Aneurysm.

Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency disorder that is characterized by a triad of microthrombocytopenia, severe immunodeficiency, and eczema. We report the case of a 7-year-old male patient with chronic thrombocytopenia that was diagnosed as WAS after dilatation of the ascending aorta was noticed. WAS is rare, and it is a disease that requires high suspicion for diagnosis. We recommend periodic echocardiography and magnetic resonance imaging examinations to evaluate aortic aneurysms in children with WAS and that surgical intervention should not be delayed when aneurysm is detected.

Clinical Features and Outcomes of 23 Patients with Wiskott-Aldrich Syndrome: A Single-Center Experience

Objective: Wiskott-Aldrich syndrome (WAS) is an X-linked primary immune deficiency characterized by microthrombocytopenia, eczema, and recurrent infections. We aimed to evaluate the clinical features and outcomes of a WAS cohort. Materials and Methods: We retrospectively evaluated the clinical courses, immunological features, treatments, and outcomes in a total of 23 WAS patients together with data related to 11 transplanted cases among them between 1982 and 2019. Results: Before admission, 11 patients (48%) were misdiagnosed with immune thrombocytopenia. WAS scores were mostly 4 or 5. Eleven patients were transplanted and they had an overall survival rate of 100% during a median follow-up period of 8.5 years (range: 8 months to 20 years). Five patients who were not transplanted died at a median of 7 years (range: 2-26 years). Nontransplanted patients had high morbidity due to organ damage, mostly caused by autoimmunity, bleeding, and infections. Two novel mutations were also defined. Conclusion: All male babies with microthrombocytopenia should be evaluated for WAS. Hematopoietic stem cell transplantation should be performed at the earliest age with the best possible donors.

Use of Thromboelastography to Guide Platelet Infusion in a Patient with Wiskott-Aldrich Syndrome Undergoing Renal Transplant.

Wiskott-Aldrich syndrome is a rare primary immuno-deficiency disorder that is characterized by a triad of microthrombocytopenia, eczema, and recurrent infections. Progression to end-stage renal failure is common in survivors due to immunoglobulin A nephropathy. We describe the case of a 24-year-old male with Wiskott-Aldrich syndrome. The patient had previous hematopoietic stem cell transplant and was on hemodialysis due to end-stage renal failure. He subsequently underwent living-donor renal transplant from his mother as the donor. This is only the fifth case of renal transplant in a patient with Wiskott-Aldrich syndrome in the world. In all cases, the perioperative management of hemostatic function has been crucial. We used thromboelastography to guide our hemostatic decisions rather than platelet count, thus reducing exposure to unnecessary platelet transfusions and without increased bleeding risk. Our patient had an uneventful course after living-donor kidney transplant.