WBR0486

Author	[[PageAuthor::Yazan Daaboul, M.D. (Reviewed by Yazan Daaboul, M.D. and Alison Leibowitz [1])]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pathophysiology, MainCategory::Pharmacology
Sub Category	SubCategory::Hematology
Prompt	[[Prompt::A 1-year-old boy is brought to the pediatrics outpatient clinic for a 4-week history of pallor and excessive sleepiness. His mother reports normal development and feeding habits. Physical examination is significant for splenomegaly and marked pallor. Work-up is remarkable for a hemoglobin level of 8.8 g/dL with hypochromia and microcytosis. Futher testing reveals a mutation in the ALAS2 gene. What is the most appropriate strategy for chronic management of this patient?]]
Answer A	AnswerA::Chronic transfusions
Answer A Explanation	[[AnswerAExp::Chronic transfusions are frequently used for the management of patients with thalassemia major or other bone marrow failure syndromes.]]
Answer B	AnswerB::Deferoxamine
Answer B Explanation	[[AnswerBExp::Deferoxamine is frequently used for the management of iron overload due to chronic transfusions. Although sideroblastic anemia is associated with iron overload due to increased transfusions and increased iron absorption, iron chelation is not usually administered chronically for patients with sideroblastic anemia.]]
Answer C	AnswerC::Vitamin B6
Answer C Explanation	[[AnswerCExp::X-linked sideroblastic anemia is frequently pyrodoxine-responsive. Patients with X-linked sideroblastic anemia are generally managed by daily pyridoxine (vitamin B6) supplementation.]]
Answer D	AnswerD::Vitamin B12
Answer D Explanation	[[AnswerDExp::Vitamin B12 supplementation is used to manage megaloblastic anemia due to vitamin B12 deficiency.]]
Answer E	AnswerE::Iron replacement
Answer E Explanation	[[AnswerEExp::Iron replacement is required for patients with iron deficiency anemia.]]
Right Answer	RightAnswer::C
Explanation	[[Explanation::Sideroblastic anemia is a heterogeneous group of disorders characterized by the presence of hypochromic microcytic erythrocytes, ineffective erythropoiesis that causes an increase in iron absorption, and mitochondrial iron accumulation in erythroid precursors of the bone marrow. X-linked sideroblastic anemia is the most common form of the disease; it is a relatively less severe form of sideroblastic anemia that is caused by mutations in the delta-aminolevulinate synthase-2 (ALAS2) gene that encodes ALA synthase, an enzyme that requires pyridoxine (vitamin B6) that catalyzes the first step in heme biosynthesis (condensation of succinyl CoA and glycine to form ALA). X-linked sideroblastic anemia may present anytime between birth and childhood. Clinical severity ranges from an asymptomatic course with incidental diagnosis to a more severe manifestation of severe pallor, fatigue, and dyspnea. Physical examination may be remarkable for pallor and mild splenomegaly. Work-up usually demonstrates microcytic anemia with an increase in reticulocyte count and elevated serum iron levels. Bone marrow aspirate is helpful and shows characteristic ringed sideroblasts. The diagnosis is confirmed by ALAS2 gene testing. Supportive care is the mainstay of management for patients with X-linked sideroblastic anemia. Patients often require frequent monitoring of hematological and iron profiles with lifetime pyridoxine supplementation. Although pyridoxine is usually helpful for patients with X-linked sideroblastic anemia, Hb levels rarely reach normal levels in these patients but is sufficient to keep patients asymptomatic and not transfusion-dependent. A minority of cases may require phlebotomies or iron chelation therapy to prevent iron overload. Prognosis depends on patient response to pyridoxine and is generally good with a normal life expectancy. Educational Objective: X-linked sideroblastic anemia is frequently pyrodoxine-responsive. Patients with X-linked sideroblastic anemia are generally managed by daily pyridoxine (vitamin B6) supplementation. References: Harris JW. X-linked, pyridoxine-responsive sideroblastic anemia. N Engl J Med. 1994;330(10):709-11. Cotter PD, Rucknagel DL, Bishop DF. X-linked sideroblastic anemia: identification of the mutation in the erythroid-specific delta-aminolevulinate synthase gene (ALAS2) in the original family described by Cooley. Blood. 1994;84:3915-24. First Aid 2014 page 383]]
Approved	Approved::Yes
Keyword	WBRKeyword::Sideroblastic anemia, WBRKeyword::Pyridoxine, WBRKeyword::Vitamin B6, WBRKeyword::Anemia, WBRKeyword::Pallor, WBRKeyword::X-linked, WBRKeyword::X-linked sideroblastic anemia
Linked Question	Linked::
Order in Linked Questions	LinkedOrder::