A 58-year-old vegetarian woman from rural Rajasthan presents with a 6-month history of progressive fatigue, dyspnea on exertion, and paresthesias in both feet. On examination, she is pale, with glossitis and a positive Romberg sign. Her hemoglobin is 7.2 g/dL. Blood smear shows macrocytic RBCs with hypersegmented neutrophils. Serum vitamin B12 is 95 pg/mL (normal >200), and serum folate is 8.5 ng/mL (normal >5.4). What is the most likely diagnosis?

Explanation

## Clinical Presentation & Diagnosis This patient presents with the classic triad of **megaloblastic anemia due to vitamin B12 deficiency**: ### Key Clinical Features **Key Point:** The combination of macrocytic anemia + neurological signs (paresthesias, positive Romberg sign) + glossitis + low B12 (95 pg/mL) is pathognomonic for B12 deficiency. ### Laboratory Findings | Parameter | Finding | Significance | |-----------|---------|---------------| | Hemoglobin | 7.2 g/dL | Moderate anemia | | Blood smear | Macrocytic RBCs + hypersegmented neutrophils | Megaloblastic morphology | | Serum B12 | 95 pg/mL (LOW) | Confirms B12 deficiency | | Serum folate | 8.5 ng/mL (NORMAL) | Excludes primary folate deficiency | **High-Yield:** Hypersegmented neutrophils (>5 lobes) are the hallmark of megaloblastic anemia and indicate impaired DNA synthesis. ### Pathophysiology of B12 Deficiency 1. B12 is essential for methylmalonyl-CoA mutase (converts methylmalonyl-CoA → succinyl-CoA) and methionine synthase (converts homocysteine → methionine) 2. Deficiency impairs DNA synthesis → megaloblastic erythropoiesis 3. Neurological complications arise from demyelination of posterior and lateral spinal cord columns (subacute combined degeneration) ### Why This Patient? **Clinical Pearl:** Vegetarian diet is a major risk factor for B12 deficiency in India, as B12 is found only in animal products. Pernicious anemia (autoimmune) is less common in this demographic. **Mnemonic for B12 deficiency causes:** **PANDA** — Pernicious anemia, Atrophic gastritis, Nitrous oxide abuse, Dietary insufficiency (vegans), Achlorhydria ### Differential Reasoning - **Folate deficiency alone:** Would present with low folate; this patient has normal folate (8.5 ng/mL) - **Combined deficiency:** Not applicable here—folate is normal - **Autoimmune hemolytic anemia:** Would show positive DAT (Coombs), elevated reticulocyte count, and elevated indirect bilirubin; this patient has a normocytic or macrocytic anemia with low reticulocytes (typical of megaloblastic anemia) [cite:Robbins 10e Ch 14]