A 57-year-old man presents with fatigue, a smooth tongue, cheilosis, and stocking-glove neuropathy. CBC shows macrocytic anemia with hypersegmented neutrophils; serum homocysteine and methylmalonic acid are elevated. What is the most likely diagnosis?

• A. Aplastic anemia
• B. Folate deficiency
• C. G6PD deficiency
• D. Pernicious anemia

Answer: (D)

The key idea is that this presentation is due to vitamin B12 deficiency causing a megaloblastic process with neurologic involvement. The combination of macrocytic anemia with hypersegmented neutrophils fits both B12 and folate deficiency, but the neurologic symptoms and the specific lab pattern point to B12 deficiency.

Stocking-glove neuropathy indicates demyelination of the peripheral nerves and spinal pathways that occurs with B12 deficiency, not with folate deficiency. The smooth tongue and cheilosis reflect mucosal changes that can accompany megaloblastic processes. Importantly, the elevated methylmalonic acid is a hallmark of B12 deficiency (folate deficiency can raise homocysteine but does not raise MMA). The presence of both elevated homocysteine and MMA, along with neurologic signs, strongly supports B12 deficiency rather than folate deficiency.

The most likely cause here is pernicious anemia, an autoimmune destruction of gastric parietal cells leading to intrinsic factor deficiency. Without intrinsic factor, B12 cannot be efficiently absorbed in the terminal ileum, producing systemic B12 deficiency with the observed findings. Aplastic anemia would present with pancytopenia and a hypocellular marrow rather than isolated macrocytosis with neuropathy, and G6PD deficiency would cause hemolysis rather than this megaloblastic picture with neurologic signs.

Treatment involves replacing B12, typically with parenteral cyanocobalamin, and evaluating for autoimmune gastritis as the underlying cause.