A 42-year-old woman from rural Maharashtra presents with a 6-month history of progressive weakness, paresthesias in her feet, and difficulty walking. On examination, she has a stocking-glove distribution of sensory loss, absent ankle reflexes, and positive Romberg's sign. Her diet consists primarily of polished rice with minimal protein intake. Blood investigations show macrocytic anemia (Hb 8.2 g/dL, MCV 108 fL) and elevated methylmalonic acid levels. What is the most likely diagnosis?

Explanation

## Clinical Diagnosis: Vitamin B12 Deficiency ### Key Clinical Features **Key Point:** The combination of macrocytic anemia, subacute combined degeneration (SCD) of the spinal cord, and elevated methylmalonic acid is pathognomonic for B12 deficiency. The patient presents with: - **Neurological manifestations:** Peripheral neuropathy (paresthesias, stocking-glove sensory loss), posterior column involvement (absent reflexes, positive Romberg's), and gait disturbance - **Hematological findings:** Macrocytic anemia with elevated MCV - **Biochemical marker:** Elevated methylmalonic acid (MMA) — a sensitive and specific marker of B12 deficiency - **Risk factor:** Poor dietary intake (polished rice, minimal protein) — common in rural populations with limited access to animal products ### Pathophysiology 1. B12 is essential for: - DNA synthesis (via methionine synthase) - Myelin formation in the nervous system - Methylation reactions 2. Deficiency leads to: - Impaired DNA synthesis → macrocytic anemia - Demyelination of posterior and lateral columns → SCD - Accumulation of methylmalonic acid and homocysteine ### Diagnostic Confirmation | Test | Finding in B12 Deficiency | |------|---------------------------| | Serum B12 | <200 pg/mL | | Methylmalonic acid | Elevated (>0.4 μmol/L) | | Homocysteine | Elevated | | Peripheral blood smear | Hypersegmented neutrophils, macro-ovalocytes | | Bone marrow | Megaloblastic changes | **High-Yield:** Elevated MMA is MORE specific for B12 deficiency than elevated homocysteine (which also rises in folate deficiency). ### Clinical Pearl Subacute combined degeneration is a medical emergency — prolonged deficiency can cause irreversible neurological damage. Early recognition and treatment are critical to prevent permanent myelopathy. **Mnemonic for B12 deficiency neurological signs:** "PVC" — Posterior columns (vibration, proprioception loss), Vertical nystagmus, Cognitive changes (dementia) ### Management - Parenteral B12 (IM injections preferred in malabsorption) - Dietary counseling (animal products, fortified foods) - Monitor neurological recovery (may be incomplete if prolonged)