PATHCHAT Edition No. 64
January 2020
Please contact your local Ampath pathologist for more information.
Authors:
- Dr. Debbie Jafta (Haematopathologist)
- Dr. Carla Griesel (Haematopathologist)
- Dr. Karen van Helden (Haematopathologist)
- Dr. Johan van Wyk (Clinical Pathologist)
Introduction
✅ Why Is Vitamin B12 Deficiency Important?
- Vitamin B12 deficiency can lead to severe disabilities, morbidity, and even death if undiagnosed.
- Early detection and treatment can reverse neurological and haematological symptoms.
- Despite being well-recognized, the diagnosis of B12 deficiency remains challenging.
📌 This publication reviews risk factors, clinical manifestations, and biomarkers used to diagnose Vitamin B12 deficiency.
Risk Factors for Developing Vitamin B12 Deficiency
✅ Who Is at Risk?
- Gastrointestinal disorders (bacterial/parasitic infections, pernicious anaemia).
- Chronic use of certain medications:
- Proton pump inhibitors (PPIs).
- Histamine H2 receptor antagonists.
- Metformin.
- Dietary factors:
- Vegetarianism or vegan diets.
- Alcoholism.
- Older age (>75 years).
📌 Risk factors must be considered in all patients with suggestive clinical features.
Manifestations of Vitamin B12 Deficiency
✅ Vitamin B12 deficiency presents with a range of symptoms:
✔ Non-Specific Symptoms:
- Glossitis (inflamed tongue).
- Skin hyperpigmentation.
- Infertility.
- Unexplained fever.
✔ Haematological Symptoms:
- Cytopenias (low blood cell counts).
- Fatigue and exertional breathlessness.
- Cardiovascular symptoms.
✔ Neurological & Psychiatric Symptoms:
- Memory loss.
- Depression.
- Alzheimer’s disease-like symptoms.
- Psychiatric disorders and psychosis.
📌 Neurological symptoms may be irreversible if deficiency is not treated early.
Biomarkers for Vitamin B12 Status and Their Limitations
✅ Laboratory Parameters Affected by B12 Deficiency:
- Increased lactate dehydrogenase (LDH) (>1,000 U/L).
- Increased bilirubin.
- Low haptoglobin.
✅ Key Biomarkers for Diagnosing Vitamin B12 Deficiency:
✔ Supporting Parameters (Non-Specific):
- Macrocytic anaemia (large red blood cells on full blood count).
- Increased lactate dehydrogenase (LDH).
- Low haptoglobin.
✔ Specific Parameters (More Reliable Indicators):
- Serum Vitamin B12 levels.
- Homocysteine levels.
- Methylmalonic acid (MMA) levels.
✅ Limitations of Biomarkers:
- Serum Vitamin B12 lacks standardized reference ranges.
- Homocysteine lacks specificity (can be elevated in folate deficiency).
- Methylmalonic acid is expensive, not widely available, and lacks specificity.
📌 A combination of tests is often required to confirm Vitamin B12 deficiency.
Proposed Diagnostic Algorithm for Vitamin B12 Deficiency
✅ Stepwise Approach to Diagnosis:
1️⃣ Evaluate Clinically:
- Assess for non-specific, haematological, or neurological symptoms.
2️⃣ Measure Serum Vitamin B12 Levels:
✔ ≥300 pmol/L:
- No deficiency—no further testing needed.
✔ 138–221 pmol/L:
- Low normal—consider further testing.
✔ 74–221 pmol/L:
- Indeterminate—test homocysteine levels.
✔ <74 pmol/L:
- Deficient—confirm diagnosis and initiate treatment.
3️⃣ Measure Homocysteine Levels (If Serum B12 is Low-Normal or Indeterminate):
✔ <15 µmol/L:
- Normal—no B12 deficiency.
✔ >15 µmol/L:
- Elevated—suggestive of B12 deficiency.
📌 Early detection using this algorithm ensures timely treatment and prevents irreversible damage.
Key Takeaways for Clinicians
✅ Vitamin B12 deficiency can cause haematological, neurological, and psychiatric complications.
✅ Risk factors include gastrointestinal disorders, medication use, dietary restrictions, and older age.
✅ Diagnosis requires a combination of serum B12, homocysteine, and methylmalonic acid levels.
✅ A stepwise approach to testing improves accuracy and prevents unnecessary treatment.
✅ Early intervention can reverse symptoms and prevent irreversible neurological damage.
📌 All tests mentioned in this publication are available at Ampath laboratories. Contact your local pathologist for cost and test availability.