WBR0641

Author	[[PageAuthor::Serge Korjian M.D. (Reviewed by Serge Korjian)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Immunology
Sub Category	SubCategory::Hematology
Prompt	[[Prompt::A 7-month-old boy is brought to the emergency room for bloody stools. The mother explains that she has been noticing blood tinged stools for the past week; but today, she noted frank blood in the diapers. On admission, the child appears well, his pulse is 123/min and his temperature is 36.8 ᵒC (98.2 ᵒF). Physical examination reveals multiple petechiae in the oral cavity. Skin inspection shows purpura most prominent on the legs and patchy eczema affecting the limbs, face, and trunk. Upon further questioning, the mother reports that the child has a history of multiple hospital admissions for recurrent respiratory tract infections. Which of the following best describes the pathophysiology of the disorder most likely present in this patient?]]
Answer A	AnswerA::Defect in DNA repair enzymes
Answer A Explanation	AnswerAExp::This defect is usually seen in patients with ataxia telangiectasia, not in WAS.
Answer B	AnswerB::T-cell inability to depolymerize cytoskeleton
Answer B Explanation	AnswerBExp::This defect is characteristic of the pathophysiology of WAS.
Answer C	AnswerC::Defect in lysosomal trafficking
Answer C Explanation	AnswerCExp::Lysosomal trafficking defects are seen in Chédiak–Higashi syndrome, not in WAS.
Answer D	AnswerD::Defect in CD40L on T-helper cells
Answer D Explanation	AnswerDExp::Defects in CD40L on T-helper cells is seen in Hyper-IgM syndrome leading to an inability to switch Ig classes. It is not seen in WAS.
Answer E	AnswerE::Defect in CD18 protein on phagocytes
Answer E Explanation	AnswerEExp::LFA-1 integrin or CD18 defect is seen in patient with leukocyte adhesion deficiency type 1 (LAD1), not in WAS.
Right Answer	RightAnswer::B
Explanation	[[Explanation::Wiskott-Aldrich Syndrome (WAS) is a rare X-linked disorder characterized by thrombocytopenia, recurrent infections, eczema, and increased risk of hematopoietic malignancies. WAS is a primary immunodeficiency syndrome with multiple affected cell lines including lymphocytes, neutrophils, and monocytes. The defect is due to a mutation in the WAS gene on the X chromosome and a defective WAS protein that combines with signaling molecules and alters the actin cytoskeleton. The WAS protein may act as support for signaling molecules in a complex cascade to regulate the cytoskeleton, or alternatively may depolymerize actin directly. Patients with WAS usually seek medical care for signs of thrombocytopenia including GI bleeding or unusual bruising. Eczema is usually an accompanying sign. Lab studies classically reveal decreased IgM levels and elevated IgE. Educational Objective: Wiskott-Aldrich Syndrome (WAS) is characterized by thrombocytopenia, recurrent infections, and eczema due to a defect in the WAS gene an important player in the cascade that regulates the cytoskeleton. References: Snapper SB, Rosen FS. The Wiskott-Aldrich syndrome protein (WASP): roles in signaling and cytoskeletal organization. Annu Rev Immunol. 1999;17:905-29.]]
Approved	Approved::Yes
Keyword	WBRKeyword::Wiskott-Aldrich Syndrome, WBRKeyword::Immunodeficiency, WBRKeyword::Eczema, WBRKeyword::Purpura, WBRKeyword::Thrombocytopenia, WBRKeyword::Immudeficiencies, WBRKeyword::Immunodeficiency syndromes
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