WBR0151

Author	PageAuthor::William J Gibson
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Genetics
Sub Category	SubCategory::Gastrointestinal, SubCategory::Hematology
Prompt	[[Prompt::A 1-year-old male is evaluated for a well-child exam. The parents report that their child has appeared listless and disengaged. He has failed to begin sitting on his own and responds poorly to verbal cues. The pediatrician notes that the patient is extremely pale. A complete blood count demonstrates a severe microcytic anemia. Hemoglobin electrophoresis shows 95% fetal hemoglobin and 5% hemoglobin alpha 2. HbS and adult hemoglobin are negative. Treatment for this child’s condition is likely to cause symptoms most similar to the genetic disease caused by mutations in which of the following?]]
Answer A	AnswerA::JAK2 gene
Answer A Explanation	[[AnswerAExp::Activating mutations in JAK2 cause polycythemia vera]]
Answer B	AnswerB::Alpha-aminolevulinic acid synthase gene
Answer B Explanation	[[AnswerBExp::Mutations in the alpha-aminolevulinic acid synthase gene cause a sideroblastic anemia.]]
Answer C	AnswerC::HFE gene
Answer C Explanation	[[AnswerCExp::Mutations in the HFE gene cause hereditary hemochromatosis. Frequent transfusions for beta-thalassemia can cause hemochromatosis.]]
Answer D	AnswerD::Porphobilinogen deaminase
Answer D Explanation	[[AnswerDExp::Mutations in the gene encoding porphobilinogen deaminase cause acute intermittent porphyria.]]
Answer E	AnswerE::ADAMTS13
Answer E Explanation	[[AnswerEExp::Antibodies against ADAMTS13 cause thrombotic thrombocytopenic purpura.]]
Right Answer	RightAnswer::C
Explanation	[[Explanation::The patient in this vignette is suffering from beta-thalassemia major. Beta thalassemia is most often caused by splice site mutations in the beta-globin gene and is prevalent in Mediterranean populations. If both alleles of the beta globin gene have thalassemia mutations, beta thalassemia major is diagnosed. This is a severe microcytic, hypochromic anemia. Untreated, it causes anemia, splenomegaly, and severe bone deformities. It often progresses to death before age 20. A hallmark feature of beta thalassemia major is the “buzz cut” or “hair on end” appearance of the skull on X-ray. This increased spiky opacity is caused by bone marrow expansion in response to chronic anemia. (extramedullary hematopoeisis). Treatment consists of periodic blood transfusion; splenectomy if splenomegaly is present, and treatment of transfusion-induced iron overload. Transfusion associated hemochromatosis is a serious complication of beta-thalassemia, but can be managed with iron chelators such as deferoxamine. Mutations of the HFE gene cause a hereditary form of hemochromatosis. Cure of beta-thalassemia is possible only by bone marrow transplantation. Educational Objective: Transfusion associated hemochromatosis is a serious complication of beta-thalassemia, but can be managed with iron chelators such as deferoxamine. Mutations of the HFE gene cause a hereditary form of hemochromatosis. References: First Aid 2014 page 383, First Aid 2012 page 381]]
Approved	Approved::Yes
Keyword	WBRKeyword::Beta thalassemia, WBRKeyword::Blood, WBRKeyword::Iron, WBRKeyword::Hemachromatosis, WBRKeyword::Transfusion, WBRKeyword::Thalassemia, WBRKeyword::Hemoglobin, WBRKeyword::Hemogloniopathy
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