WBR0479

Author	[[PageAuthor::Yazan Daaboul, M.D. (Reviewed by Yazan Daaboul, M.D.)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Immunology, MainCategory::Pathology
Sub Category	SubCategory::Head and Neck
Prompt	[[Prompt::A 5-month-old boy is brought to the physician's office for recurrent infections. Following appropriate work-up, the patient is diagnosed with an inherited X-linked disease that results in a defective interleukin (IL)-2 receptor and is referred to bone marrow transplantation (BMT). Which of the following findings on physical examination is most likely associated with the patient's condition?]]
Answer A	AnswerA::Absent pus formation
Answer A Explanation	[[AnswerAExp::Absent pus formation is observed among patients with leukocyte adhesion deficiency (LAD).]]
Answer B	AnswerB::Partial albinism
Answer B Explanation	[[AnswerBExp::Partial albinism is observed among patients with Chediak-Higashi syndrome.]]
Answer C	AnswerC::Retained primary teeth
Answer C Explanation	[[AnswerCExp::Retained primary teeth is observed among patients with Job's syndrome (Hyper IgE syndrome).]]
Answer D	AnswerD::Cleft palate
Answer D Explanation	[[AnswerDExp::DiGeorge syndrome is a CATCH-22 syndrome that is associated with cleft palate. The classical features of DiGeorge syndrome include: Cardiac anomalies such as Tetralogy of Fallot, abnormal facies, thymic aplasia or hypoplasia, cleft lip/palate, and hypocalcemia due to hypoparathyroidism.]]
Answer E	AnswerE::Oral thrush
Answer E Explanation	[[AnswerEExp::Oral thrush is caused by oral candidiasis, which is often present among patients with SCID due to absence of T-cell lymphocytes.]]
Right Answer	RightAnswer::E
Explanation	[[Explanation::Severe combined immunodeficiency (SCID) is a X-linked cellular and humoral immunodeficiency syndrome caused by mutations in the IL2RG gene that encodes a cytokine receptor gamma chain. The mutation results in deficiency/absence of T-lymphocytes, B-lymphocytes, and natural killer (NK) cells. Patients are generally male infants due to the X-linked pattern of inheritance, and they typically present within the first 3-6 months of age. Signs and symptoms typically include failure to thrive, recurrent infections including fungal and opportunistic infections (e.g. candida in oral/diaper region or Pneumocystis pneumonia), and absent tonsils and lymph nodes. In USA, some states recommend newborn screening for X-SCID. Additional testing includes lymphocyte counts, flow cytometry which demonstrates the lymphocyte subset enumeration, and molecular genetic testing for IL2RG gene. Lymph node biopsy demonstrates absence of germinal centers. Because T-cells are deficient/absent, patients will have thymic hypoplasia that is manifested as an absent thymic shadow on chest x-ray. Thymic function testing demonstrates deficient thymopoiesis due to deficient T-cell receptor excision circles (TRECs). The only curative option for patients with X-SCID is bone marrow transplantation, but recently, gene therapy has been investigated. Other causes of SCID include adenosine deaminase (ADA) deficiency that may cause a spectrum of clinical disease that includes any of the following 4 phenotypes: SCID, less severe CID, late/adult onset CID, or benign partial ADA deficiency with normal immune function. ADA deficiency is usually caused by deletions of the ADA gene, which is inherited in an autosomal recessive pattern. Accordingly, SCID due to ADA deficiency should be distinguished from X-SCID caused by IL2RG mutation based on genetic testing, the pattern on inheritance, and spectrum of clinical severity. Educational Objective: X-SCID is caused by absence of T-lymphocytes, B-lymphocytes, and natural killer (NK) cells. Signs and symptoms typically include failure to thrive, recurrent infections including fungal and opportunistic infections (e.g. candida in oral/diaper region or Pneumocystis pneumonia), absent tonsils and lymph nodes, and absence of thymic shadow on chest x-ray. References: Allenspach E, Rawlings DJ, Scharenberg AM. X-Linked Severe Combined Immunodeficiency. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 2003. Hershfield M. Adenosine Deaminase Deficiency. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 2006. First Aid 2014 page 213]]
Approved	Approved::Yes
Keyword	WBRKeyword::SCID, WBRKeyword::Severe combined immunodeficiency, WBRKeyword::X-SCID, WBRKeyword::IL2RG, WBRKeyword::Immunity, WBRKeyword::Immunodeficiency, WBRKeyword::Oral thrush, WBRKeyword::Recurrent infections, WBRKeyword::X-linked, WBRKeyword::Adenosine deaminase deficiency
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