Vitamin B12 and Folate Deficiency: Lab Diagnosis
Vitamin B12 (cobalamin) and Folate (vitamin B9) are essential micronutrients required for DNA synthesis, red blood cell formation, and neurological function. Their deficiency can cause megaloblastic anemia, neuropathy, and elevated cardiovascular risk.
🔬 Pathophysiology
Both Vitamin B12 and Folate are coenzymes in the conversion of homocysteine to methionine and are essential for thymidine synthesis. Deficiency impairs DNA synthesis, leading to ineffective hematopoiesis and macrocytosis.
🧪 Laboratory Diagnosis Overview
- Serum Vitamin B12
- Serum and RBC Folate
- Methylmalonic Acid (MMA)
- Total Homocysteine
- Complete Blood Count (CBC)
- Peripheral Blood Smear
📊 Diagnostic Algorithm
Step 1: Check CBC → Macrocytic anemia (MCV > 100 fL)?
Step 2: Measure Serum B12 and Folate
Step 3: If B12 is borderline (200–350 pg/mL), test MMA and Homocysteine
📋 Reference Ranges and Interpretation
| Test | Normal Range | Deficiency Indicator |
|---|---|---|
| Serum Vitamin B12 | 200–900 pg/mL | <200 pg/mL (definite) |
| Serum Folate | 3.1–17.5 ng/mL | <3 ng/mL |
| RBC Folate | 140–628 ng/mL | <140 ng/mL |
| Methylmalonic Acid (MMA) | 0.00–0.40 µmol/L | >0.40 µmol/L |
| Homocysteine | 4–12 µmol/L | >12 µmol/L |
🔍 Functional Tests: MMA & Homocysteine
Homocysteine: Elevated in both folate and B12 deficiency.
🧬 Blood Smear & Bone Marrow Findings
- Macro-ovalocytes
- Hypersegmented neutrophils
- Increased LDH and indirect bilirubin (hemolysis)
- Megaloblastic maturation in bone marrow
⚠️ Causes of Deficiency
Vitamin B12 Deficiency
- Pernicious anemia (anti-IF antibodies)
- Gastrectomy, bariatric surgery
- Chronic use of PPIs or metformin
- Vegan diet
Folate Deficiency
- Alcoholism
- Malnutrition
- Malabsorption (celiac disease)
- Pregnancy
- Antifolate drugs: Methotrexate, phenytoin
🧠 Neurological Manifestations
Vitamin B12 deficiency can lead to subacute combined degeneration of the spinal cord (posterior column + corticospinal tract), manifesting as:
- Gait ataxia
- Paresthesia
- Memory impairment
💉 Treatment Monitoring
- Repeat B12/Folate after 4–8 weeks of supplementation
- Check reticulocyte count for early response (within 7 days)
- Neurological improvement may take weeks to months
📚 Related Articles
- Lab Diagnosis of Megaloblastic Anemia
- Understanding RBC Indices (MCV, MCH, MCHC)
- Homocysteine: A Marker for Cardiovascular and Nutritional Disorders
❓ Frequently Asked Questions (FAQs)
1. Can I have normal B12 but still be deficient?
Yes. In borderline levels (200–350 pg/mL), functional tests like MMA and homocysteine are necessary.
2. Is B12 or folate deficiency more common?
Folate deficiency is more common in populations with poor diet and alcohol use, while B12 deficiency is rising due to vegan diets and PPI overuse.
3. Does folate supplementation mask B12 deficiency?
Yes, it can correct anemia while allowing neurological damage to progress. Always check B12 status before treating with folate alone.
📌 Conclusion
Accurate laboratory diagnosis of Vitamin B12 and folate deficiency is crucial to prevent irreversible neurological damage and treat macrocytic anemia. Incorporating serum tests, functional markers, and clinical correlation ensures a holistic approach.
Tags: Vitamin B12 Test, Folate Deficiency Test, MMA, Homocysteine, CBC Interpretation, Macrocytic Anemia, Lab Diagnosis
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