A 38-year-old woman from rural Maharashtra presents with a 6-month history of progressive weakness, numbness in her feet, and difficulty walking. On examination, she has a stocking-glove distribution of sensory loss, diminished deep tendon reflexes in the lower limbs, and a positive Romberg sign. Her diet consists mainly of polished rice and legumes with minimal vegetables or animal products. Hemoglobin is 9.2 g/dL, and peripheral blood smear shows macrocytic RBCs. Serum vitamin B12 level is 180 pg/mL (normal >200). What is the most likely diagnosis?

Explanation

## Clinical Presentation Analysis The patient presents with a classic triad of neurological manifestations of vitamin B12 deficiency: ### Key Neurological Features - **Sensory neuropathy**: Stocking-glove distribution of sensory loss - **Proprioceptive loss**: Positive Romberg sign indicates dorsal column involvement - **Diminished reflexes**: Suggests posterior and lateral column degeneration **Key Point:** This constellation of peripheral neuropathy + dorsal column signs + lateral corticospinal tract involvement is pathognomonic for subacute combined degeneration (SCD) of the spinal cord, the hallmark neurological manifestation of B12 deficiency [cite:Park 26e Ch 9]. ### Laboratory Confirmation - **Macrocytic anemia**: RBC indices show macrocytosis (characteristic of B12 and folate deficiency) - **Low B12 level**: 180 pg/mL is below the normal threshold of 200 pg/mL - **Dietary risk**: Polished rice diet (low B12 sources) + vegetarian pattern + no animal products ### Why B12 and Not Folate? | Feature | B12 Deficiency | Folate Deficiency | |---------|---|---| | **Neurological signs** | Present (SCD, neuropathy, cognitive changes) | Absent | | **Dorsal column involvement** | Yes (paresthesias, ataxia, Romberg+) | No | | **Dietary source** | Animal products, fortified foods | Leafy greens, legumes | | **Anemia pattern** | Macrocytic + neurological | Macrocytic only | **Clinical Pearl:** Folate deficiency causes megaloblastic anemia but does NOT cause neurological symptoms; B12 deficiency causes both. The presence of SCD clinches the diagnosis [cite:Harrison 21e Ch 99]. ### Pathophysiology of SCD ```mermaid flowchart TD A[Vitamin B12 Deficiency]:::outcome --> B[Impaired Myelin Synthesis]:::outcome B --> C[Degeneration of Dorsal Columns]:::action B --> D[Degeneration of Lateral Corticospinal Tracts]:::action C --> E[Loss of Proprioception & Vibration Sense]:::outcome D --> F[Weakness & Hyperreflexia]:::outcome E --> G[Ataxia, Romberg Sign Positive]:::outcome F --> G ``` **High-Yield:** B12 is essential for methylation reactions and myelin formation. Deficiency leads to demyelination of the spinal cord (hence "combined" degeneration of multiple tracts) [cite:KD Tripathi 8e Ch 24]. ### Management Implications - **Urgent treatment**: B12 supplementation (IM cyanocobalamin 1000 mcg weekly × 6 weeks, then monthly maintenance) - **Prognosis**: Early treatment can reverse neurological symptoms; delayed treatment may cause permanent spinal cord damage - **Screening**: Check folate levels simultaneously; if folate is also low, supplement both to avoid masking B12 deficiency with folate monotherapy