A 60-year-old presents with fatigue and macrocytic anemia with hypersegmented neutrophils. What is the most likely deficiency and the initial confirmatory test?

• A. Vitamin B12 deficiency; measure serum B12 and methylmalonic acid
• B. Folate deficiency; measure serum folate
• C. Iron deficiency; measure ferritin
• D. Copper deficiency; measure ceruloplasmin

Answer: (A)

Macrocytic (megaloblastic) anemia with hypersegmented neutrophils signals defective DNA synthesis, most often from a deficiency of vitamin B12 or folate. In a 60-year-old, vitamin B12 deficiency is the more likely cause, commonly due to pernicious anemia or malabsorption.

The best initial confirmatory step is to measure serum B12 level to detect deficiency. If B12 is low or borderline, checking methylmalonic acid is helpful because MMA accumulates when B12 is deficient (independent of folate status). An elevated MMA with a low B12 level confirms B12 deficiency and differentiates it from folate deficiency, which would not raise MMA.

Iron deficiency would produce microcytic anemia, making it less likely here. Copper deficiency is a rarer cause and not specifically tied to this pattern of macrocytosis with hypersegmented neutrophils.