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GMC Kadapa 2025 - Case Analysis
1. Diagnosis: Megaloblastic Anemia due to Vitamin B12 (Cobalamin) Deficiency
Clinical clues pointing to this diagnosis:
| Feature | Significance |
|---|---|
| Indigestion, diarrhea | GI involvement (B12 affects gut epithelium) |
| Angular stomatitis, sore mouth | Epithelial/mucosal change |
| Red beefy tongue (glossitis) | Classic sign of B12/folate deficiency |
| Tingling in hands and feet | Peripheral neuropathy |
| MCV: 100 fL | Macrocytosis (MCV >100 = macrocytic anemia) |
| MCH: 50 pg | Elevated (normal 27-33 pg) - hypochromic RBCs? Actually elevated MCH suggests macrocytes |
| Hb: 9 g% | Anemia confirmed |
| RBC: 1 million/cu.mm | Very low (normal ~4.5-5.5 million) |
| Reticulocyte count: 6% | Elevated - indicates ineffective erythropoiesis / hemolysis component |
| S.Iron: 170 µg/dL (within normal) | Excludes iron-deficiency anemia |
The elevated MCV (macrocytosis), combined with the neurological features and glossitis, confirms megaloblastic anemia - and the presence of peripheral neuropathy points specifically to Vitamin B12 deficiency rather than folate deficiency (folate deficiency causes megaloblastic anemia but does NOT cause peripheral neuropathy).
"In addition to megaloblastic anemia, vitamin B12 deficiency often causes myeloneuropathy, the combination of spinal cord disease and peripheral neuropathy." - Frameworks for Internal Medicine
2. Cause of Peripheral Neuropathy in Vitamin B12 Deficiency
The mechanism is demyelination of the nervous system. Specifically:
Biochemical basis:
- Vitamin B12 is required as a cofactor for methionine synthase, which converts homocysteine to methionine
- Methionine is needed for the synthesis of S-adenosylmethionine (SAM), the universal methyl donor
- SAM is required for methylation of myelin basic protein and phospholipids essential for myelin sheath synthesis and maintenance
- B12 deficiency disrupts this pathway → defective myelin production → demyelination
Pathological change:
- This leads to subacute combined degeneration (SCD) of the spinal cord - affecting:
- Posterior columns (loss of vibration and proprioception)
- Lateral (corticospinal) tracts (spasticity, weakness)
- Peripheral nerves (tingling, numbness - as seen in this patient)
Clinical features of the neuropathy:
- Paresthesias in extremities (tingling in hands and feet - as in this case)
- Sensory loss, ataxia
- Lower limb weakness, spasticity
- Hyporeflexia or hyperreflexia (e.g., brisk patellar reflex with diminished Achilles reflex)
- Cognitive impairment (in severe/prolonged cases)
The classic "five P's" of B12 deficiency include: Pancytopenia, Peripheral neuropathy, Posterior column degeneration, Papillary (tongue) atrophy, and Pyramidal tract signs - Swanson's Family Medicine Review
"Vitamin B12 deficiency causes myelopathy, encephalopathy, optic neuropathy, peripheral neuropathy, or some combination of these disorders. The neurological complications do not necessarily correlate with the presence or severity of associated megaloblastic anemia." - Bradley and Daroff's Neurology in Clinical Practice
3. Causes and Treatment of Vitamin B12 Deficiency Megaloblastic Anemia
CAUSES:
A. Decreased Intake (Dietary)
- Strict vegan / vegetarian diet - B12 is found exclusively in animal products (meat, poultry, fish, shellfish, eggs, dairy)
- Elderly patients on restricted diets ("tea and toast")
- Malnutrition / poverty
B. Malabsorption (Most Common Category)
| Cause | Mechanism |
|---|---|
| Pernicious anemia (most common overall) | Autoimmune destruction of gastric parietal cells → lack of intrinsic factor (IF) → B12 cannot be absorbed in terminal ileum |
| Atrophic gastritis / H. pylori infection | Reduced gastric acid and IF production |
| Total / subtotal gastrectomy | Loss of parietal cells → no IF |
| Terminal ileum disease (Crohn's disease, resection) | Site of B12-IF complex absorption lost |
| Pancreatic insufficiency | Pancreatic proteases needed to release B12 from R-proteins |
| Celiac disease / IBD | Mucosal damage impairing absorption |
| Fish tapeworm (Diphyllobothrium latum) | Competes for dietary B12 |
| Alcoholism | Impairs absorption and utilization |
C. Increased Demand
- Pregnancy and breastfeeding
- Hyperthyroidism
- Chronic hemolytic anemia
D. Drugs
- Metformin (reduces B12 absorption via calcium-dependent mechanism)
- Proton pump inhibitors / H2 blockers (reduce gastric acid needed for B12 release from food)
- Nitrous oxide (inactivates methionine synthase)
TREATMENT:
1. Correct the underlying cause (e.g., treat H. pylori, manage celiac disease, stop offending drugs)
2. Vitamin B12 Replacement:
| Route | Regimen | Indication |
|---|---|---|
| Intramuscular (IM) / Subcutaneous | 1000 mcg/day for 1 week, then weekly for 1 month, then 1000 mcg/month for life | Pernicious anemia, post-gastrectomy (cannot absorb oral B12) |
| Oral | 1000-2000 mcg/day | Dietary deficiency, when absorption is intact |
- High-dose oral B12 works even in pernicious anemia through passive (non-IF-mediated) absorption at ~1% of dose
- Response to treatment: Reticulocytosis peaks at 5-7 days, Hb normalizes in 6-8 weeks, neurological recovery is slower and may be incomplete if severe
3. Supportive:
- Folic acid should NOT be given alone without B12, as it can correct the anemia but worsen neurological damage (masks deficiency while neuropathy progresses)
- Dietary counseling for vegans; supplementation with B12-fortified foods
Sources: Yamada's Textbook of Gastroenterology, 7th ed. | Frameworks for Internal Medicine | Swanson's Family Medicine Review | Bradley and Daroff's Neurology in Clinical Practice
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