WBR0151
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| Author | [[PageAuthor::William J Gibson (Reviewed by Yazan Daaboul, M.D.)]] |
|---|---|
| Exam Type | ExamType::USMLE Step 1 |
| Main Category | MainCategory::Genetics |
| Sub Category | SubCategory::Gastrointestinal, SubCategory::Hematology |
| Prompt | [[Prompt::A 1-year-old boy is brought by his parents for failure to thrive. The parents report that their child appears listless and disengaged. He has failed to begin sitting on his own and responds poorly to verbal cues. On physical examination, the pediatrician notes that the patient is very pale. A complete blood count demonstrates Hb=7.2 g/dL and MCV=71 fLa. Hemoglobin electrophoresis demonstrates absent HbA, elevated HbA2 and HbF, and negative HbS. Chronic 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 (''ALAS2'') gene |
| Answer B Explanation | [[AnswerBExp::Mutations in the ALAS2 gene, which encodes alpha-aminolevulinic acid synthase, cause 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 secondary hemochromatosis.]] |
| Answer D | AnswerD::Porphobilinogen (PBG) deaminase gene |
| Answer D Explanation | [[AnswerDExp::Mutations in the gene that encodes porphobilinogen deaminase cause acute intermittent porphyria.]] |
| Answer E | AnswerE::''ADAMTS13'' gene |
| Answer E Explanation | [[AnswerEExp::Mutations of the ADAMTS13 gene cause congenital thrombotic thrombocytopenic purpura (TTP). On the other hand, development of antibodies against ADAMTS13 cause acquired thrombotic thrombocytopenic purpura.]] |
| Right Answer | RightAnswer::C |
| Explanation | [[Explanation::Beta thalassemia is a hereditary hemoglobinopathy that is commonly caused by splice site mutations that result in deficiency in beta-globin hemoglobin chains. It is prevalent among Mediterranean populations. Beta-thalassemia is a severe microcytic, hypochromic anemia. Clinical manifestations of beta-thalassemia include anemia with ineffective erythropoiesis, hepatosplenomegaly, and severe bone deformities. Patients with thalassemia major are considered transfusion-dependent because they require chronic blood transfusions to survive. Nonetheless, chronic transfusions are accompanied by severe life-threatening complications, such as transfusion-transmitted infections such as viral hepatitis B and C, and iron overload, which is believed to be caused by 2 factors: First, hemosiderosis associated with the transfusions; and second, the paradoxically excessive GI iron absorption due to the presence of a humoral factor that down-regulates hepcidin which normally inhibits iron absorption. Iron overload may result in iron deposition in organs, such as the heart, the liver, and endocrine gland that lead to organ failure. To prevent complications such as cardiotoxicity, iron chelat2qion by deferoxamine, deferiprone, or deferasirox. Although chronic transfusions are needed for survival of patients with beta-thalassemia major, the only cure for these patients is bone marrow transplantation. 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 secondary hemochromatosis is a serious complication of beta-thalassemia and other diseases that require chronic transfusions. Iron overload can be managed by iron chelators such as deferoxamine. Mutations in the HFE gene cause a hereditary form of hemochromatosis. |
| Approved | Approved::Yes |
| Keyword | WBRKeyword::Beta thalassemia, WBRKeyword::Blood, WBRKeyword::Iron, WBRKeyword::Hemachromatosis, WBRKeyword::Transfusion, WBRKeyword::Thalassemia, WBRKeyword::Hemoglobin, WBRKeyword::Hemogloniopathy |
| Linked Question | Linked:: |
| Order in Linked Questions | LinkedOrder:: |