Wiskott-Aldrich Syndrome (WAS): Pathogenesis and clinical findings X-linked recessive inheritance (mostly males impacted) Spontaneous DNA mutation
Genetic mutations in Wiskott-Aldrich Syndrome Protein (WASP) impair actin cytoskeleton remodeling in hematopoietic cells (immature blood cells)
Authors: Mina Mina Reviewers: Hana Osman Mao Ding Maharshi Gandhi Shahab Marzoughi Louis-Philippe Girard* * MD at time of publication
Megakaryocytes (platelet precursor cells) depend on the cytoskeleton changing shape to form pseudopodia (arm-like projections) which bud off forming cellular fragments (platelets)
Abnormal cytoskeleton reorganization leads to ineffective thrombocytopoiesis (production of platelets)
Microthrombocytopenia (↓ platelet size and quantity)
Issues with formation of a platelet plug due to abnormal platelets (dysfunction of primary hemostasis)
Reduced ability for platelet adhesion, activation, and/or aggregation
Natural killer cells depend on the cytoskeleton reorganization to form immunological synapses (communication) with body cells in order to have effective surveillance
T cells depend on the cytoskeleton remodeling to form pseudopods which allow them to synapse with other cells when a pathogen is encountered
Defective immune synapse formation
↓ Cancer immunosurveillance
↑ Risk of malignancy
Helper T cells cannot activate B cells which generate antibodies (immunoglobulins) to destroy pathogens
Regulatory T cells can not sufficiently downregulate effector cells which typically limit the immune response and prevent autoimmune conditions
↑ Risk of autoimmune diseases
Recurrent opportunistic infections
Immune dysregulation
Impaired immune response
↓ Number and function of T cells
Immune responses contribute to Type 2 immune responses
Atopic dermatitis (AD; chronic inflammation that causes itchy skin)
↑ Immunoglobulin (Ig) A
Epistaxis (nosebleed)
Red blood cells leak from capillaries
Menorrhagia (heavy menstrual bleeding)
Petechiae (small, flat, red spots that appear on the skin)
Inflammation in AD triggers release of interleukins (modulatory proteins during inflammatory and immune responses) leading to Immunoglobulin (Ig) class switching
↑ IgE levels
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Pathophysiology
Mechanism
Sign/Symptom/Lab Finding
Complications
Published Apr 20, 2024 on www.thecalgaryguide.com