Vitamin B12 Deficiency
Summary
Vitamin B12 (Cobalamin) deficiency is a major cause of macrocytic anaemia and potentially irreversible neurological damage. The leading cause in developed nations is Pernicious Anaemia (Autoimmune Metaplastic Atrophic Gastritis), but dietary deficiency (Veganism) and drug causes (Metformin/PPIs) are increasing. It presents with a classic triad of Fatigue, Glossitis (Beefy tongue), and Neuropathy (Symmetical dorsal column loss). [1,2]
Clinical Pearls
The Folate Trap: NEVER replace Folate before checking B12.
- If a patient has B12 deficiency but you treat them with Folic Acid, their anaemia will cure (because folate bypasses the DNA trap), but their neurological degeneration will accelerate.
- Always treat B12 before or with Folate.
Neuro without Anaemia: 20-30% of patients with B12 deficiency have normal Haemoglobin and normal MCV. If clinical suspicion is high (paraesthesia, ataxia), check B12 regardless of the FBC.
Lemon Yellow Skin: The combination of Anaemia (Pallor) + Mild Haemolysis (Jaundice) gives the patient a characteristic "LemonTinge".
Demographics
- Prevalence: Increases with age (10% of >75s).
- Risk Groups:
- Pernicious Anaemia: Northern European / Autoimmune Hx (Thyroid/Vitiligo). Female > Male.
- Dietary: Vegans (no animal products).
- Malabsorption: Crohn's, Ileal Resection, Coeliac.
- Drugs: Metformin (long term), PPIs.
Absorption Pathway (The Complex Journey)
- Mouth: Haptocorrin binds B12.
- Stomach: Parietal cells secrete Intrinsic Factor (IF). Acid is needed to split B12 from food.
- Duodenum: Pancreatic enzymes degrade Haptocorrin, allowing B12 to bind IF.
- Terminal Ileum: B12-IF complex is absorbed via Cubilin receptors.
Mechanism of Disease
- DNA Synthesis: B12 is a co-factor for converting Homocysteine to Methionine. Failure leads to arrest of DNA synthesis -> Megaloblastic Anaemia (Large immature red cells, Hypersegmented neutrophils).
- Myelin: B12 prevents accumulation of Methylmalonic Acid (MMA), which is toxic to myelin. Failure leads to Demyelination of the spinal cord (Dorsal Columns + Corticospinal Tracts).
| Condition | MCV | Features |
|---|---|---|
| B12 Deficiency | >100 | Neuropathy, Glossitis. |
| Folate Deficiency | >100 | No neuro signs. Dietary history. |
| Alcohol / Liver | >100 | Target cells. Elevated GGT. |
| Hypothyroidism | >100 | Cold/Weight gain. |
| MDS | >100 | Dysplasia, Elderly. |
Haematological
Neurological (SACD - Subacute Combined Degeneration)
First Line
- FBC: Low Hb, High MCV (>110 common).
- Blood Film: Hypersegmented Neutrophils (>5 lobes) are pathognomonic. Oval Macrocytes.
- Biochemistry:
- Serum B12: Low (less than 150 ng/L). Note: False normals exist (inactive B12 analogues).
- Folate: Often raised (Folate trap).
Second Line (If B12 Borderline)
- Methylmalonic Acid (MMA): Elevated (Sensitive).
- Homocysteine: Elevated (Non-specific).
- Autoantibodies:
- Anti-Intrinsic Factor: Highly Specific (95%) for Pernicious Anaemia. Low Sensitivity (50%).
- Anti-Parietal Cell: Sensitive (90%) but Non-Specific (seen in 10% of normals).
Management Algorithm
CONFIRMED B12 DEFICIENCY
↓
PRESENCE OF NEURO SIGNS?
┌─────────┴─────────┐
YES NO
(Intensive) (Standard)
↓ ↓
HYDROXOCOBALAMIN HYDROXOCOBALAMIN
1mg IM on 1mg IM
Alternate Days 3 times/week
until no further for 2 weeks
improvement
↓ ↓
MAINTENANCE MAINTENANCE
1mg IM every 1mg IM every
2 months 3 months
Oral Replacement
- Cyanocobalamin (Oral): Only suitable for Dietary prevention (Vegans). Not sufficient for Pernicious Anaemia or Malabsorption (as they cannot absorb oral forms effectively).
Associated Conditions
- Check Thyroid (TSH) and Coeliac screen (IgA-tTG) due to autoimmune clustering.
- Gastric Cancer: Pernicious Anaemia is a risk factor for Gastric Carcinoma (2-3x risk). Low threshold for undetected gastric malignancy if new symptoms arise.
- Permanent Neurology: If treatment is delayed >6 months, cord damage may not reverse.
- Infertility.
- Anaemia: Responds rapidly (Reticulocyte count peaks in 7 days). Hb normalises in 2 months.
- Neurology: Improvement is slow (months). Residual ataxia/paraesthesia is common if diagnosis was delayed.
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| B12/Folate | BSH (2014) | Guidelines on diagnosis (MMA) and treatment regimens. |
| Investigation | NICE CKS | Algorithm for replacement. |
Landmark Evidence
1. Stabler (NEJM 2013)
- Comprehensive review clarifying the metabolic basis (MMA/Homocysteine) and the limitations of serum B12 testing alone.
What is B12 Deficiency?
Vitamin B12 is essential for making healthy red blood cells and for keeping your nerves insulated. Because B12 is only found in animal products (meat/dairy), or requires a special acid system in your stomach to absorb, deficiencies are common.
What is Pernicious Anaemia?
It sounds scary, but it just means your immune system has attacked the stomach lining cells that help you absorb B12. It is not cancer, but it means you cannot absorb B12 from food, no matter how much steak you eat.
Why do I need injections?
Because your stomach cannot absorb the vitamin from food or tablets, we have to bypass the stomach and inject it directly into the muscle.
Symptoms
You might feel incredibly tired, have a sore red tongue, or feel "pins and needles" in your hands and feet. If left untreated, it can make you unsteady on your feet.
Is it for life?
Usually yes. If you have Pernicious Anaemia, you will need an injection every 3 months forever. It is a very effective and safe treatment.
Primary Sources
- Devalia V, et al. Guidelines for the diagnosis and treatment of cobalamin and folate disorders. Br J Haematol. 2014.
- Stabler SP. Vitamin B12 deficiency. N Engl J Med. 2013.
- Green R. Vitamin B12 deficiency from the perspective of a practicing hematologist. Blood. 2017.
Common Exam Questions
- Diagnosis: "Macrocytic anaemia + Hypersegmented Neutrophils?"
- Answer: B12/Folate Deficiency.
- Safety: "Treatment of dual deficiency?"
- Answer: B12 first, then Folate.
- Autoimmunity: "Antibody for Pernicious Anaemia?"
- Answer: Anti-Intrinsic Factor (Specific).
- Neurology: "Loss of vibration + UMN signs?"
- Answer: Subacute Combined Degeneration of the Cord.
Viva Points
- Why Jaundice?: It is an "intramedullary haemolysis". The red cells are so badly formed they die inside the bone marrow before being released, spilling bilirubin.
- Schilling Test: Historically used to differentiate causes (radioactive B12). No longer used. Replaced by antibody testing.
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.