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 stocking-glove sensory loss, absent ankle reflexes, and a positive Romberg sign. Her diet consists mainly of polished rice and legumes with minimal animal products. Blood pressure is 110/70 mmHg. Serum vitamin B12 level is 180 pg/mL (normal >200). What is the most likely diagnosis?

Explanation

## Clinical Presentation Analysis **Key Point:** The combination of peripheral neuropathy (stocking-glove sensory loss, absent reflexes) with posterior column involvement (positive Romberg sign, gait ataxia) in a patient with borderline-low B12 and a vegetarian diet is pathognomonic for subacute combined degeneration (SCD). ## Pathophysiology of B12 Deficiency 1. **Demyelination mechanism**: Vitamin B12 is essential for myelin synthesis via methylmalonyl-CoA mutase and methionine synthase pathways 2. **Dorsal column involvement**: Posterior and lateral columns of the spinal cord degenerate (hence "combined") 3. **Peripheral nerve involvement**: Distal sensory nerves affected early 4. **Cognitive changes**: May progress to subacute combined degeneration with dementia if untreated ## Diagnostic Criteria Met | Feature | Present | Significance | |---------|---------|---------------| | Stocking-glove sensory loss | Yes | Peripheral neuropathy | | Absent ankle reflexes | Yes | Lower motor neuron involvement | | Positive Romberg | Yes | Dorsal column (proprioception) loss | | Vegetarian diet | Yes | Risk factor for B12 deficiency | | Serum B12 180 pg/mL | Yes | Borderline deficient (cutoff ~200) | | Progressive 6-month course | Yes | Subacute presentation | **High-Yield:** SCD is a medical emergency—neurological damage may become irreversible if B12 replacement is delayed beyond 6–12 months of symptom onset. ## Differential Exclusion **Diabetic neuropathy**: No mention of diabetes, hyperglycemia, or diabetic retinopathy; Romberg sign is not typical of pure diabetic neuropathy. **Thiamine deficiency**: Presents with Wernicke triad (ophthalmoplegia, ataxia, confusion) or Korsakoff syndrome; no mention of alcohol abuse or acute encephalopathy. **Vitamin E deficiency**: Rare, causes spinocerebellar degeneration in malabsorption (cystic fibrosis, abetalipoproteinemia); no history of malabsorption; B12 level is the key clue here. **Clinical Pearl:** Serum B12 levels 200–300 pg/mL are "gray zone"—if clinical suspicion is high, check methylmalonic acid (MMA) and homocysteine levels; elevated MMA and homocysteine confirm functional B12 deficiency even if serum B12 is borderline. ## Management IM vitamin B12 1000 µg weekly for 8 weeks, then monthly maintenance. Neurological recovery is best if initiated within the first 6–12 months.