Which laboratory finding is most characteristic of vitamin B12 deficiency causing macrocytic anemia?

• A. Increased methylmalonic acid
• B. Increased ferritin
• C. Decreased homocysteine
• D. Hemolysis markers elevated

Answer: (A)

Vitamin B12 deficiency impairs the enzyme that converts methylmalonyl-CoA to succinyl-CoA, a step that directly requires B12. Without this cofactor, methylmalonyl-CoA builds up and is converted to methylmalonic acid, so the level of methylmalonic acid rises in blood and urine. This rise is highly characteristic of B12 deficiency causing macrocytic (megaloblastic) anemia and helps distinguish it from folate deficiency, where methylmalonic acid remains normal even though homocysteine may be elevated in both conditions. Ferritin elevation is not specific to B12 deficiency, and hemolysis markers aren’t a feature of macrocytic anemia due to defective DNA synthesis.