What are the signs of Vitamin B12 (Vit B12) deficiency?

Signs and Symptoms of Vitamin B12 Deficiency

Vitamin B12 deficiency presents with a spectrum of hematologic, neurologic, and dermatologic manifestations that can become permanent if left untreated for more than 3 months. 1, 2

Clinical Manifestations

Hematologic Signs

• Megaloblastic anemia
• Macrocytosis
• Hypersegmented neutrophils
• Pancytopenia in severe cases

Neurological Manifestations

• Subacute combined degeneration of the spinal cord (progressive weakness, numbness, ataxia)
• Peripheral neuropathy (paresthesias, numbness)
• Loss of joint position sense and vibration sense
• Positive Romberg's sign
• Absent or diminished deep tendon reflexes, particularly ankle jerks 3
• Cognitive impairment and memory problems
• Headaches (particularly common in adolescents) 4
• Developmental delay (in infants) 4
• Seizures (in infants) 4

Dermatologic and Mucosal Signs

• Pallor due to anemia
• Hyperpigmentation (particularly on palms and soles) 3
• Glossitis (smooth, red, sore tongue)
• Angular cheilitis (cracks at corners of mouth)

Other Manifestations

• Fatigue and weakness
• Anorexia
• Dizziness
• Tachycardia
• Shortness of breath (due to anemia)
• Irritability and mood changes
• Infertility

High-Risk Groups

Screening for vitamin B12 deficiency should be considered in:

• Older adults (especially those >75 years)
• Patients with gastric or small intestine resections
• Patients with ileal resection >20 cm (mandatory lifelong supplementation) 1
• Patients with inflammatory bowel disease
• Patients taking metformin for >4 months
• Patients taking proton pump inhibitors or H2 blockers for >12 months
• Vegans or strict vegetarians
• Pregnant or lactating women
• Patients with pernicious anemia 5

Diagnostic Approach

Initial Testing

• Total serum B12 (cobalamin) or active B12 (holotranscobalamin)
  • <180 ng/L (total B12) or <25 pmol/L (active B12): Confirmed deficiency
  • 180-350 ng/L (total B12) or 25-70 pmol/L (active B12): Indeterminate

  • 350 ng/L (total B12) or >70 pmol/L (active B12): Unlikely deficiency 1

• Complete blood count

Confirmatory Testing (for indeterminate results)

• Methylmalonic acid (MMA) - elevated in B12 deficiency
• Homocysteine levels - elevated in B12 deficiency
• Folate levels (to rule out concurrent deficiency)
• Iron studies 1, 6

Important Clinical Considerations

1. Early detection is crucial - Vitamin B12 deficiency that progresses for more than 3 months may cause permanent degenerative lesions of the spinal cord 2

2. Folic acid caution - Doses of folic acid >0.1 mg/day may mask hematologic manifestations of B12 deficiency while allowing neurological damage to progress 2

3. Monitoring response - During initial treatment, monitor:

   • Serum potassium (first 48 hours)
   • Hematocrit and reticulocyte counts (daily from days 5-7, then periodically until normalized)
   • B12 levels periodically during maintenance therapy 1, 2

4. Holotranscobalamin (holoTC) is the earliest laboratory marker for B12 deficiency, while methylmalonic acid (MMA) is a functional marker that increases when B12 stores are depleted 6

5. Neurological symptoms may be present even with normal hematologic parameters, and can be irreversible if treatment is delayed 4, 3

6. Vitamin B12 deficiency can contribute to geriatric syndromes including frailty, falls, cognitive impairment, and malnutrition 7

By recognizing these signs and symptoms early and initiating prompt treatment, irreversible neurological damage can be prevented in patients with vitamin B12 deficiency.