A 58-year-old Indian woman presents with a 3-month history of progressive fatigue, dyspnea on exertion, and paresthesias in both feet. She is a strict vegetarian who avoids dairy products. On examination, she has glossitis, mild jaundice, and a positive Romberg sign. Blood investigations reveal hemoglobin 7.2 g/dL, MCV 118 fL, reticulocyte count 0.8%, serum vitamin B12 level 95 pg/mL (normal >200), and serum folate 8.2 ng/mL (normal >5.4). Peripheral blood smear shows hypersegmented neutrophils and oval macrocytes. Bone marrow aspiration shows megaloblastic erythropoiesis with giant metamyelocytes. What is the most likely diagnosis?

Explanation

## Clinical Diagnosis: Vitamin B12 Deficiency Anemia ### Key Clinical Features **Key Point:** The combination of megaloblastic anemia WITH neurological manifestations (paresthesias, positive Romberg sign suggesting posterior column involvement) is pathognomonic for vitamin B12 deficiency. ### Laboratory Findings Analysis | Parameter | Finding | Interpretation | |-----------|---------|----------------| | **Hemoglobin** | 7.2 g/dL | Moderate anemia | | **MCV** | 118 fL | Macrocytic (>100 fL) | | **Serum B12** | 95 pg/mL | **Markedly low** (<200 pg/mL) | | **Serum folate** | 8.2 ng/mL | **Normal** (>5.4 ng/mL) | | **Reticulocyte count** | 0.8% | Inappropriately low (suggests ineffective erythropoiesis) | **High-Yield:** The **normal serum folate with low B12** is the diagnostic differentiator. In pure folate deficiency, folate levels would be low. ### Pathophysiology of B12 Deficiency 1. **Megaloblastic changes**: B12 is essential for DNA synthesis (methionine synthase pathway); deficiency causes nuclear maturation lag while cytoplasmic maturation continues → nuclear-cytoplasmic asynchrony 2. **Neurological manifestations**: B12 deficiency causes demyelination of posterior and lateral columns (subacute combined degeneration) → paresthesias, ataxia, positive Romberg sign 3. **Glossitis & jaundice**: Due to ineffective erythropoiesis and hemolysis from abnormal RBCs ### Peripheral Blood & Bone Marrow Findings **Key Point:** Hypersegmented neutrophils (≥6 lobes) and oval macrocytes on blood smear are hallmark findings of megaloblastic anemia. **Clinical Pearl:** Giant metamyelocytes in bone marrow are pathognomonic for megaloblastic erythropoiesis — these are abnormally large, immature myeloid precursors with open chromatin pattern. ### Risk Factor in This Patient Strict vegetarian diet avoiding dairy = **dietary B12 deficiency**. Vitamin B12 is found only in animal products (meat, eggs, dairy). This is the most common cause of B12 deficiency in vegetarians in India [cite:Harrison 21e Ch 110]. ### Why Neurological Signs Matter **Warning:** Folate supplementation alone in B12 deficiency can mask anemia while neurological damage progresses irreversibly. This patient requires B12 replacement urgently.