Vitamin B12 Deficiency
Definition | Aetiology | Pathophysiology | Risk Factors | Signs and Symptoms | Investigations | Management
Definition
Vitamin B12 deficiency is a condition resulting from inadequate levels of vitamin B12, leading to impaired DNA synthesis, haematological abnormalities, and neurological dysfunction.
Aetiology
- Pernicious anaemia: autoimmune destruction of gastric parietal cells leading to intrinsic factor deficiency.
- Dietary deficiency: common in vegans and those with poor nutritional intake.
- Malabsorption: gastric bypass surgery, coeliac disease, Crohn’s disease.
- Drug-induced: metformin, proton pump inhibitors (PPIs), H2-receptor antagonists.
- Increased demand: pregnancy, chronic haemolysis.
Pathophysiology
- Vitamin B12 is required for DNA synthesis and myelin formation.
- Deficiency leads to ineffective erythropoiesis, causing megaloblastic anaemia.
- Neurological complications arise due to impaired methylation of myelin proteins.
Risk Factors
- Strict vegan diet.
- History of gastrointestinal surgery or disorders.
- Long-term use of metformin or PPIs.
- Age over 65 years.
- Autoimmune conditions (e.g., type 1 diabetes, thyroid disease).
Signs and Symptoms
- Fatigue, pallor.
- Glossitis, angular cheilitis.
- Neurological symptoms: paraesthesia, numbness, peripheral neuropathy.
- Neuropsychiatric changes: memory impairment, depression.
- Gait disturbance, ataxia.
Investigations
- Full blood count (FBC): macrocytic anaemia.
- Blood film: hypersegmented neutrophils.
- Serum vitamin B12: low levels confirm deficiency.
- Intrinsic factor antibodies: positive in pernicious anaemia.
- Methylmalonic acid and homocysteine: elevated in B12 deficiency.
- Coeliac screen: if malabsorption is suspected.
Management
Vitamin B12 Management Summary
- Indication for Checking B12: Anaemia or strong clinical suspicion (e.g., visual disturbance, memory loss, psychiatric abnormalities, peripheral nerve dysfunction without other identifiable cause).
B12 Level Interpretation:
- ≥180 ng/L & No Symptoms: No further investigation.
- 145-179 ng/L:
- If asymptomatic → Continue dietary control, no further action or they can purchase Oral cyanocobalamin 50-150mcg daily.
- If strong clinical suspicion persists → Check Intrinsic Factor Antibody (IFAB).
- <145 ng/L: Check IFAB but proceed to treatment regardless.
IFAB Testing Outcomes:
- Positive: Confirmed pernicious anaemia.
- Negative: Consider dietary deficiency.
Management Based on Symptoms:
- No Neurological Symptoms:
- Initial: IM Hydroxocobalamin 1mg three times a week for 2 weeks.
- Maintenance:
- Dietary cause: Oral cyanocobalamin 50-150mcg daily (OTC).
- Non-dietary: IM Hydroxocobalamin 1000mcg every 3 months for life.
- Neurological Symptoms:
- Seek Specialist Advice (including IFAB result).
- Immediate treatment while awaiting advice: IM Hydroxocobalamin 1mg every other day until no symptoms.
- Maintenance: IM Hydroxocobalamin 1000mcg every 2-3 months for life (or as per specialist recommendation).
Specialist Advice Guidance:
- Consult appropriate specialist (Gastro, Neurology, Elderly Care).
- Remote advice usually sufficient.
- Use NHS advice & guidance platforms if available.
- Consider haematology referral if Hb does not improve.
1. Vitamin B12 Replacement:
- Hydroxocobalamin 1 mg IM injections: loading dose (3 times a week for 2 weeks), then maintenance every 3 months.
- Oral cyanocobalamin: for dietary deficiency in non-neurological cases.
2. Treat Underlying Cause:
- Manage malabsorptive conditions (e.g., treat coeliac disease, adjust medications affecting absorption).
- Lifelong supplementation in pernicious anaemia.
3. Referral:
- Haematology: for severe cases or unclear aetiology.
- Gastroenterology: if malabsorption or coeliac disease is suspected.
- Neurology: if neurological deficits persist despite treatment.