WBR0321

Author	[[PageAuthor::Yazan Daaboul, M.D. (Reviewed by Serge Korjian)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Biochemistry
Sub Category	SubCategory::General Principles
Prompt	[[Prompt::A 5-year-old boy is diagnosed with a disorder characterized by the deficiency of enzyme X. The enzyme is an essential component of the pathway shown below. Which of the following is most likely to be a clinical feature of this patient's condition? ]]
Answer A	AnswerA::Delayed separation of umbilical cord
Answer A Explanation	AnswerAExp::Leukocyte adhesion deficiency (type I) is due to a defect in LFA-1 integrin. Patients typically present with recurrent bacterial infections with no pus formation and delayed separation of the umbilical cord.
Answer B	AnswerB::Absence of germinal centers on lymph node biopsy
Answer B Explanation	AnswerBExp::Absence of germinal centers on lymph node biopsy due to absence of B cells is found in SCID.
Answer C	AnswerC::Thrombocytopenic purpura and eczema
Answer C Explanation	AnswerCExp::Thrombocytopenic purpura, eczema, and infections are found in patients with Wiskott-Aldrich syndrome, caused by inability of T-cell reorganization of actin cytoskeleton.
Answer D	AnswerD::Self-mutilation and choreoathetosis
Answer D Explanation	AnswerDExp::Self-mutilation and choreoathetosis are found in patients with Lesch-Nyhan syndrome, caused by a deficiency of HGPRT.
Answer E	AnswerE::Precipitation of monosodium urate crystals in joints on arthrocentesis
Answer E Explanation	AnswerEExp::Gout is caused by precipitation of monosodium urate crystals (MSU) in joints. It is a common complication of hyperuricemia.
Right Answer	RightAnswer::B
Explanation	[[Explanation::Adenosine deaminase deficiency, the likely culprit in this patient, is an important cause of severe combined immunodeficiency (SCID). SCID is a syndrome encompassing a group of rare congenital disorders characterized by B cell and T cell deficiency. All forms of SCID are inherited, most common of which is X-linked. X-linked SCID is caused by a deficiency of IL-2 receptor gamma leading to a failure in the development and differentiation of T and B cells. Adenosine deaminase deficiency is the second most common cause of SCID. Adenosine deaminase is coded for by a gene on chromosome 20 and is essential for the breakdown of purines. Loss of this enzyme leads to the accumulation of dATP causing feedback inhibit the activity of ribonucleotide reductase. As ribonucleotide reductase is essential for dNTP synthesis, DNA replication would cease and lymphocyte proliferation is subsequently inhibited. Accordingly, patients with SCID present early in childhood with failure to thrive and recurrent infections by viruses, bacteria and fungi. Work-up may reveal thymic aplasia and loss of germinal centers on lymph node biopsy. Currently, the only curative treatment for SCID is bone marrow transplantation despite several controversial attempts at introducing gene therapy as an alternative (mainly due to the high incidence of leukemias). Educational Objective: Adenosine deaminase deficiency is a common cause of severe combined immunodeficiency (SCID). References: Weinberg K, Parkman R. Severe combined immunodeficiency due to a specific defect in the production of interleukin-2. N Engl J Med. 1990;322(24):1718-23. Parkman R, Gelfand EW, Rosen FS, Sanderson A, Hirschhorn R. Severe combined immunodeficiency and adenosine deaminase deficiency. N Engl J Med. 1975;292(14):714-9. First Aid 2014 page 68.]]
Approved	Approved::Yes
Keyword	WBRKeyword::SCID, WBRKeyword::Severe combined immunodeficiency, WBRKeyword::IL-2 receptor gamma, WBRKeyword::ADA, WBRKeyword::Adenosine deaminase deficiency, WBRKeyword::Autosomal recessive, WBRKeyword::Congenital immunodeficiencies, WBRKeyword::B-cell, WBRKeyword::T-cell, WBRKeyword::Bubble boy syndrome
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