-
Expert Review of Clinical Immunology 2015Wiskott-Aldrich syndrome is a life-threatening primary immunodeficiency associated with a bleeding tendency, eczema and a high incidence of autoimmunity and malignancy.... (Review)
Review
Wiskott-Aldrich syndrome is a life-threatening primary immunodeficiency associated with a bleeding tendency, eczema and a high incidence of autoimmunity and malignancy. Stem cell transplantation offers the opportunity of cure for all these complications, and over the past 35 years there has been a remarkable improvement in survival following this treatment. Here, we review advances in management of clinical complications pre- and post-transplant, as well as discuss the morbidity Wiskott-Aldrich syndrome patients experience following treatment. For patients with a poorly matched stem cell donor, recent gene therapy trials demonstrate encouraging results and the potential of low-toxicity therapy for all patients.
Topics: Child, Preschool; Genetic Predisposition to Disease; Genetic Therapy; Hematopoietic Stem Cell Transplantation; Humans; Infant; Mutation; Survival Analysis; Wiskott-Aldrich Syndrome; Wiskott-Aldrich Syndrome Protein
PubMed: 26159751
DOI: 10.1586/1744666X.2015.1062366 -
Scientific Reports Feb 2021Wiskott Aldrich syndrome (WAS) is a rare disease and hematopoietic stem cell transplant (HCT) is considered the treatment modality of choice for WAS. We conducted a...
Wiskott Aldrich syndrome (WAS) is a rare disease and hematopoietic stem cell transplant (HCT) is considered the treatment modality of choice for WAS. We conducted a cross-sectional analysis on the KIDS' pediatric inpatient database and compared hospitalization rates, complications and healthcare utilizations in the transplant and non-transplant arms. Of the 383 pediatric admissions with diagnosis of WAS between 2006-2012, 114 underwent transplant and 269 did not. The non-transplant arm included older children, female patients and more African Americans. Death rates, income and payer source were similar in both arms, however the total charge for each admission was higher in the transplant arm. Emergency room visits were similar but non-elective admissions were more in the non-transplant arm. Length of stay was prolonged in the transplant arm. When comparing morbidities, lymphomas, ulcerative colitis and autoimmune complications of WAS were seen only in the non-transplant arm. Our study shows that transplant is the largest contributor to healthcare utilization in WAS patients. We identified healthcare disparities based on race and socioeconomic status and found that this rare disease is being appropriately directed to centers with HCT expertise. We noted a change in practice moving away from splenectomy in WAS patients.
Topics: Child, Preschool; Female; Healthcare Disparities; Hematopoietic Stem Cell Transplantation; Hospital Mortality; Humans; Male; Population Groups; Social Class; Wiskott-Aldrich Syndrome
PubMed: 33633315
DOI: 10.1038/s41598-021-84328-0 -
Pediatric Dermatology Sep 1991
Topics: Humans; Infant; Male; Wiskott-Aldrich Syndrome
PubMed: 1745637
DOI: 10.1111/j.1525-1470.1991.tb00872.x -
Archives of Disease in Childhood Dec 1967
Topics: Blood Cell Count; Eczema; Humans; Infant, Newborn; Isoantibodies; Male; Melena; Pedigree; Sex Factors; Wiskott-Aldrich Syndrome
PubMed: 6073827
DOI: 10.1136/adc.42.226.604 -
Clinical and Experimental Immunology Feb 2005
Review
Topics: B-Lymphocytes; Humans; Mutation; Proteins; T-Lymphocytes; Wiskott-Aldrich Syndrome; Wiskott-Aldrich Syndrome Protein
PubMed: 15654814
DOI: 10.1111/j.1365-2249.2005.02707.x -
Indian Pediatrics Nov 1995
Review
Topics: Bone Marrow Transplantation; Child, Preschool; Combined Modality Therapy; Diagnosis, Differential; Humans; Male; Wiskott-Aldrich Syndrome
PubMed: 8772876
DOI: No ID Found -
Indian Pediatrics Dec 2014Wiskott-Aldrich syndrome is a rare X-linked immunodeficiency disorder with a variable phenotype.
BACKGROUND
Wiskott-Aldrich syndrome is a rare X-linked immunodeficiency disorder with a variable phenotype.
CASE CHARACTERISTICS
3.5-year-old boy diagnosed with Wiskott-Aldrich syndrome.
OBSERVATION
Unusual and persistent thrombocytopenia with increased platelet volume (>10fL). He did not exhibit characteristic clinical and laboratory finding for the syndrome.
OUTCOME
Maternally inherited causative mutation in the exon 2 of the WAS gene was disclosed.
MESSAGE
This is a need for multidisciplinary assessment of patients with congenital or early infantile thrombocytopenia, including testing for mutations of the WAS gene in all unexplained cases even in the absence of characteristic microthrombocytopenia.
Topics: Humans; Infant; Male; Thrombocytopenia; Wiskott-Aldrich Syndrome; Wiskott-Aldrich Syndrome Protein
PubMed: 25560165
DOI: 10.1007/s13312-014-0550-5 -
Biology of Blood and Marrow... Jan 2009Wiskott-Aldrich syndrome (WAS) is a rare X-linked immunodeficiency disorder that has a variable clinical phenotype that correlates with the type of mutation in WASP, the... (Review)
Review
Wiskott-Aldrich syndrome (WAS) is a rare X-linked immunodeficiency disorder that has a variable clinical phenotype that correlates with the type of mutation in WASP, the gene encoding the WAS protein (WASP). WASP is a key regulator of actin polymerization in hematopoietic cells and has well-defined domains that are involved in signaling, cell locomotion, and immune synapse formation. Classic WAS often results from mutations that cause the absence of WASP expression, associated with thrombocytopenia with small platelets, sinopulmonary infections, and eczema in young males. Other phenotypes associated with expression of mutated WASP are X-linked thrombocytopenia and neutropenia. To date, the only curative therapy for WAS is hematopoietic cell transplantation (HCT) although gene therapy for WAS is under study. At least 2 retrospective studies of HCT for WAS have indicated that although HLA-matched sibling donors have the best outcomes (81% to 88%), when such a donor is not available, a matched unrelated donor should be considered (71% event free survival), although results are best in patients age < 5 years. Whereas most of the experience to date in Asia, Europe, and North America has been with myeloablative conditioning regimens, more recently, reduced-intensity conditioning (RIC) regimens also have been used with success. The issue of whether mixed chimerism post-HCT (which has a higher incidence in RIC transplantation) is associated with increased autoimmune manifestations in patients with WAS remains to be resolved.
Topics: Hematopoietic Stem Cell Transplantation; Humans; Treatment Outcome; Wiskott-Aldrich Syndrome; Wiskott-Aldrich Syndrome Protein
PubMed: 19147084
DOI: 10.1016/j.bbmt.2008.10.007 -
Current Opinion in Immunology Aug 1998Wiskott-Aldrich syndrome is an X-linked disorder characterized by thrombocytopenia, eczema and immunodeficiency. The Wiskott-Aldrich syndrome protein and the gene that... (Review)
Review
Wiskott-Aldrich syndrome is an X-linked disorder characterized by thrombocytopenia, eczema and immunodeficiency. The Wiskott-Aldrich syndrome protein and the gene that encodes it have been identified by positional cloning and the protein has been shown to contain a pleckstrin-homology domain, a GTPase-binding domain, a proline-rich region and a verprolin/cofilin homology domain. Subsequent studies suggest that the protein is involved in signal transduction and the regulation of the cytoskeleton.
Topics: Animals; Humans; Mice; Proteins; Wiskott-Aldrich Syndrome; Wiskott-Aldrich Syndrome Protein
PubMed: 9722916
DOI: 10.1016/s0952-7915(98)80113-1 -
Pediatrics International : Official... Jan 2016Wiskott-Aldrich syndrome (WAS) is an X-linked primary immunodeficiency disease characterized by recurrent infection, thrombocytopenia, and eczema. The gene responsible... (Review)
Review
Wiskott-Aldrich syndrome (WAS) is an X-linked primary immunodeficiency disease characterized by recurrent infection, thrombocytopenia, and eczema. The gene responsible for X-linked WAS encodes the Wiskott-Aldrich syndrome protein (WASP), which is expressed in hematopoietic cells and which regulates T-cell activation and cytoskeletal reorganization in T-cell receptor (TCR) signaling. Here, I review my recent research on WASP and the WASP-interacting protein (WIP) complex in T cells. I and my colleagues first established a diagnostic screening method using flow cytometry and genetic analysis, and elucidated the molecular pathogenesis in WAS patients with unique clinical manifestations. We investigated the mechanisms by which WASP is recruited to lipid rafts following TCR stimulation and to immunological synapses between antigen-presenting cells and T cells. Subsequently, we elucidated the molecular mechanisms by which WASP is degraded by calpain and ubiquitinated by Cbl-family proteins, which terminate WASP activation. More importantly, we found that WIP plays a critical role in WASP stability in T cells. These results provide new insights into the molecular pathogenesis of X-linked WAS and have facilitated the identification of WIP deficiency as an autosomal recessive form of WAS.
Topics: Humans; Signal Transduction; Wiskott-Aldrich Syndrome; Wiskott-Aldrich Syndrome Protein
PubMed: 26331277
DOI: 10.1111/ped.12819