A 62-year-old man comes to the office due to 2 months of progressive weakness, fatigue, and dyspnea on exertion. His daughter adds that he has not taken care of himself since his wife's death a year ago and spends most of his time alone drinking alcohol. Physical examination shows mucosal pallor and several petechiae. Laboratory results are as follows: Peripheral blood smear results are shown below.
Which of the following is the most likely cause of this patient's condition?

Question

A 62-year-old man comes to the office due to 2 months of progressive weakness, fatigue, and dyspnea on exertion.  His daughter adds that he has not taken care of himself since his wife's death a year ago and spends most of his time alone drinking alcohol.  Physical examination shows mucosal pallor and several petechiae.  Laboratory results are as follows:  Peripheral blood smear results are shown below.
 Which of the following is the most likely cause of this patient's condition?

Quizplus · Accepted Answer

Explanation: This patient has symptomatic anemia with macrocytic red blood cells, hypersegmented neutrophils, and normal methylmalonic acid level indicating folate deficiency. Folate is obtained from nutritional sources such as meats and leafy vegetables. Unlike cobalamin (vitamin B₁₂), body stores of folate are minimal, and deficiency occurs quickly if dietary intake wanes. This is rare in developed countries due to the fortification of flour with folic acid; however, patients with severe alcohol abuse and poor nutrition may become deficient in as little as 5-6 weeks. ₁₂ Both folate and cobalamin deficiency impair DNA synthesis in cells with rapid turnover. Manifestations most commonly arise in the hematopoietic cells of the bone marrow and include: Megaloblastic anemia - macrocytic (mean corpuscular volume >100 µm³) red blood cells with peripheral smear evidence of hypersegmented neutrophils Low/normal reticulocyte count - inability to increase red blood cell production to respond to anemia Pancytopenia - if deficiency is severe Hyperhomocysteinemia - decreased metabolism of homocysteine Unlike cobalamin deficiency (Choice A), folate deficiency is associated with normal methylmalonic acid levels and no neurologic manifestations. (Choices C and F) Cobalamin deficiency may occur with intestinal bacterial overgrowth (competes for cobalamin) or pernicious anemia (lack of intrinsic factor). Cobalamin deficiency typically takes years (not months) to develop, and the methylmalonic acid level would be high (not normal). (Choice D) Myelodysplasia is a hematopoietic neoplasm that may cause macrocytic anemia with thrombocytopenia and leukopenia. However, peripheral blood smear usually shows dysplastic granulocytes that are hypogranulated and hyposegmented (not hypersegmented). (Choice E) Pancreatic insufficiency reduces the absorption of fat-soluble vitamins (A, D, E, and K). Although vitamin K deficiency may impair the coagulation pathway (eg, bruising, petechiae) and vitamin E deficiency may cause hemolytic anemia, neither results in megaloblastic anemia. Educational objective: Body stores of folate are minimal, and deficiency may occur quickly in the setting of significant alcohol abuse. Folate and cobalamin (vitamin B₁₂) deficiencies both result in megaloblastic anemia with insufficient reticulocytosis, but folate deficiency is associated with normal (not high) methylmalonic acid levels. ₁₂

A 62-Year-Old Man Comes to the Office Due to 2