Quick Reference
Symptom patterns and diagnostic clusters for B12 deficiency.
Symptom Clusters
Neurological Cluster
Suggests subacute combined degeneration or peripheral neuropathy
Key Features
- •Peripheral paraesthesia (hands/feet)
- •Loss of vibration sense
- •Proprioceptive loss
- •Ataxic gait
- •Positive Romberg sign
- •Cognitive impairment
🚨 Red Flags
- • Rapidly progressive weakness
- • Bladder/bowel dysfunction
Action
Treat urgently without waiting for results if neurological symptoms present
Haematological Cluster
Classic megaloblastic anaemia presentation
Key Features
- •Macrocytic anaemia (MCV >100 fL)
- •Fatigue
- •Pallor
- •Glossitis
- •Angular stomatitis
- •Hypersegmented neutrophils
🚨 Red Flags
- • Severe anaemia (Hb <70)
- • Pancytopenia
Action
Check B12, folate, reticulocytes; consider haematology referral if pancytopenia
GI/Malabsorption Cluster
Suggests pernicious anaemia or malabsorption cause
Key Features
- •History of autoimmune conditions
- •Atrophic gastritis
- •Previous gastric surgery
- •Coeliac disease
- •Crohn's disease (terminal ileum)
- •Bacterial overgrowth
🚨 Red Flags
- • Weight loss
- • GI bleeding
Action
Consider intrinsic factor antibodies; may need lifelong replacement
Drug-Induced Risk Cluster
Medication-related B12 depletion
Key Features
- •Long-term metformin use (>3 years)
- •Proton pump inhibitor use
- •H2 receptor antagonist use
- •Nitrous oxide exposure (including recreational)
- •Colchicine
- •Anticonvulsants
🚨 Red Flags
- • Acute N2O toxicity
- • Metformin + declining renal function
Action
Annual B12 monitoring for at-risk medications; acute N2O requires urgent treatment
Diagnostic Tests at a Glance
| Test | Interpretation |
|---|---|
| Serum B12 | <150 ng/L: Deficient | 150-300: Borderline | >300: Likely adequate |
| MCV | >100 fL suggests macrocytosis (but can be normal in early deficiency) |
| MMA | Elevated >0.4 μmol/L suggests tissue deficiency (more sensitive than serum B12) |
| Homocysteine | Elevated in both B12 and folate deficiency (less specific) |
| IF Antibodies | Positive in ~50-70% pernicious anaemia (high specificity, low sensitivity) |
| Holotranscobalamin | Active B12; may detect early deficiency before serum B12 falls |