WBR0485
| Author | [[PageAuthor::Rim Halaby, M.D. [1]]] |
|---|---|
| Exam Type | ExamType::USMLE Step 1 |
| Main Category | MainCategory::Pathology, MainCategory::Pathophysiology |
| Sub Category | SubCategory::Hematology |
| Prompt | [[Prompt::An 18 month old boy was brought to an outpatient hematology department with complaints of pallor since birth. The child had a history of several hospital admissions for severe pallor and had been receiving blood transfusions every couple of months as of 2 months of age. History was negative for fever, bleeding, or jaundice. He had met all his milestones and was developing normally. The patient's family had recently migrated from Pakistan, and the mother denies any similar manifestations in the family. On physical exam, the physician notices pallor, frontal bossing, and hepatomegaly 4 cm below the costal margin. Exam was negative for icterus, lymphadenopathy, cyanosis, or clubbing. Blood work-up is significant for anemia (Hb= 6.7 g/dL) and the findings on blood smear shown below. What is the most likely mutation associated with the patient's condition? |
| Answer A | AnswerA::HbA Alpha-chain mutation |
| Answer A Explanation | AnswerAExp::Alpha chain mutations are seen in alpha-thalassemia and do not cause ringed sideroblasts on blood smear. |
| Answer B | AnswerB::HbA Beta-chain mutation |
| Answer B Explanation | AnswerBExp::Beta chain mutations are seen in beta-thalassemia and do not cause ringed sideroblasts on blood smear. |
| Answer C | AnswerC::Delta-ALA synthase mutation |
| Answer C Explanation | AnswerCExp::Delta-ALA synthase mutations particularly X-linked ALAS2 gene mutations are responsible for congenital sideroblastic anemia. |
| Answer D | AnswerD::Spectrin and Ankyrin mutations |
| Answer D Explanation | AnswerDExp::Spectrin and Ankyrin mutations are seen in hereditary sperocytosis and do not cause ringed sideroblasts on blood smear. |
| Answer E | AnswerE::Glucose-6-Phosphate Dehydrogenase mutaion |
| Answer E Explanation | AnswerEExp::Glucose-6-Phosphate Dehydrogenase mutations are seen in G6PD deficiency and do not cause ringed sideroblasts on blood smear. |
| Right Answer | RightAnswer::C |
| Explanation | [[Explanation::Congenital sideroblastic anemia is an inherited disease characterized by hypochromic microcytic anemia, iron overload, and ringed sideroblasts on blood smear and bone marrow biopsy. Although the inheritance pattern can be very heterogeneous, the most common presentation is X-linked secondary to a mutation in the ALAS2 gene producing a defective ALA synthase enzyme. Since ALA synthase catalyses the first step in heme synthesis, deficiency leads to a decrease in heme synthesis and mitochondrial iron accumulation manifesting as ringed sideroblasts. The anemia usually responds to oral vitamin B6 in most patients as pyridoxine is a key cofactor in the ALAS reaction. In general, the age at presentation, the severity of anemia, and the response to vitamin B6 are variable. Diagnosis depends on bone marrow biopsy or smear, HPLC, and blood iron work-up. Prussian blue staining is often needed to detect the iron rings. Prussian blue involves a non-enzymatic reaction of ferrous iron with ferrocyanide forming ferric-ferrocyanide, which is blue in color.
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| Approved | Approved::No |
| Keyword | WBRKeyword::Sideroblastic anemia, WBRKeyword::Sideroblasts, WBRKeyword::ALA synthase mutation |
| Linked Question | Linked:: |
| Order in Linked Questions | LinkedOrder:: |
