A 42-year-old male construction worker from rural Maharashtra presents with a 3-month history of progressive numbness and tingling in his feet, followed by weakness in his legs. On examination, he has diminished vibration and proprioception sense in the lower limbs, brisk reflexes, and a positive Romberg sign. His diet consists mainly of polished rice and minimal protein intake. Blood pressure is 128/82 mmHg. Serum vitamin B₁₂ level is 450 pg/mL (normal: 200–900). MRI spine shows no cord compression. Which vitamin deficiency is most likely responsible for his neurological manifestations?

Explanation

## Clinical Presentation Analysis The patient presents with a classic triad of **peripheral neuropathy + dorsal column signs (vibration/proprioception loss) + ataxia (Romberg sign)** in the setting of a diet heavy in polished rice and minimal protein — a hallmark of **thiamine (vitamin B₁) deficiency**. ## Thiamine Deficiency: Dry Beriberi **Key Point:** Thiamine is a cofactor for pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, and transketolase. Its deficiency impairs carbohydrate metabolism and myelin synthesis, causing selective damage to the peripheral nervous system and dorsal columns. ### Neurological Manifestations of Thiamine Deficiency | Feature | Dry Beriberi | Wet Beriberi | |---------|--------------|---------------| | **Presentation** | Peripheral neuropathy, dorsal column signs, ataxia | High-output cardiac failure, pulmonary edema | | **Sensory Loss** | Vibration, proprioception (dorsal columns) | Present but secondary | | **Motor Signs** | Distal weakness, foot drop, hyperreflexia | Cardiogenic shock | | **Romberg Sign** | Positive (dorsal column involvement) | Absent | | **Risk Factor** | Polished rice, alcohol, malnutrition | Wet rice diet, high carbohydrate load | **High-Yield:** Polished rice is the classic risk factor in India and Southeast Asia because the thiamine-rich bran and germ are removed during processing. ## Why Dorsal Column Signs Occur 1. Thiamine is essential for myelin synthesis via transketolase-dependent pentose phosphate pathway 2. Dorsal columns (fasciculus gracilis and cuneatus) are most metabolically active and vulnerable 3. Results in selective loss of vibration and proprioception ("sensory ataxia") **Clinical Pearl:** The combination of **peripheral neuropathy + dorsal column signs + ataxia** in a malnourished patient is pathognomonic for thiamine deficiency. The normal B₁₂ level rules out cobalamin deficiency. ## Thiamine Cofactor Roles **Mnemonic:** **TPPP** — Transketolase, Pyruvate dehydrogenase, α-Ketoglutarate dehydrogenase, Phosphoketolase All are carbohydrate metabolism enzymes. When thiamine is deficient, these pathways fail, leading to: - Impaired energy production in high-demand tissues (nervous system, heart) - Accumulation of pyruvate and lactate (lactic acidosis in severe cases) - Reduced NADPH production (impaired myelin synthesis) **Tip:** In exam vignettes, look for the **diet history** — polished rice, alcohol, or hyperalimentation without thiamine supplementation are the key clues.