How to diagnose vitamin B12 deficiency in children under 2 years?

Diagnosing Vitamin B12 Deficiency in Children Under 2 Years

The diagnosis of vitamin B12 deficiency in children under 2 years should include serum total B12 (with values <180 ng/L indicating confirmed deficiency) or active B12 (holotranscobalamin) testing, along with methylmalonic acid (MMA) and homocysteine levels, complete blood count, and assessment of neurological symptoms. 1

Clinical Presentation in Infants Under 2 Years

Vitamin B12 deficiency in infants presents with distinctive clinical features:

• Neurological manifestations:

  • Developmental delay or regression 2, 3
  • Hypotonia (present in all affected infants in some studies) 3
  • Seizures (observed in approximately 47% of cases) 3
  • Tremors (observed in about 33% of cases) 3
  • Lethargy 2

• General symptoms:

  • Failure to thrive 2
  • Anorexia and pallor 3
  • Vomiting 2

Diagnostic Approach

Laboratory Testing

1. Initial screening:

   • Serum total B12 (cobalamin) or active B12 (holotranscobalamin) 1
     • Confirmed deficiency: Total B12 <180 ng/L or active B12 <25 pmol/L
     • Indeterminate: Total B12 180-350 ng/L or active B12 25-70 pmol/L
     • Unlikely deficiency: Total B12 >350 ng/L or active B12 >70 pmol/L

2. Confirmatory tests (especially for indeterminate results):

   • Methylmalonic acid (MMA) - elevated in B12 deficiency 1, 2
   • Homocysteine - elevated in B12 deficiency 1, 2
   • Complete blood count - may show megaloblastic anemia 4, 3
   • Red blood cell indices (MCV, RDW) - macrocytosis may be present 4

3. Additional testing:

   • Folate levels (to rule out concurrent deficiency) 1
   • Reticulocyte count 4
   • Percentage of hypochromic red cells 4
   • Reticulocyte hemoglobin 4

Risk Assessment

Identify potential causes of B12 deficiency in infants:

• Exclusively breastfed infants of B12-deficient mothers (most common cause) 2
• Maternal vegan/vegetarian diet during pregnancy and lactation 2
• Maternal pernicious anemia 1
• Maternal history of gastric surgery or inflammatory bowel disease 1
• Infant malabsorption disorders 1

Interpretation of Results

• A comprehensive diagnosis should integrate laboratory findings with clinical presentation
• Neurological symptoms in infants with confirmed low B12 levels strongly suggest B12 deficiency
• The presence of elevated MMA and homocysteine with low B12 confirms metabolic B12 deficiency 1, 2

Important Considerations and Pitfalls

• Early diagnosis is critical: Delayed diagnosis can lead to permanent neurological damage 2, 5
• Maternal assessment: Always evaluate maternal B12 status and diet in breastfed infants with suspected deficiency 2
• Normal hemoglobin doesn't rule out deficiency: Neurological symptoms can precede hematological abnormalities 3
• Potential for misdiagnosis: Symptoms like developmental delay or seizures may be attributed to other conditions if B12 deficiency isn't considered 3, 5
• Treatment response: Clinical improvement after B12 supplementation supports the diagnosis 5

Follow-up Testing

• Monitor response to treatment through:
  • Clinical neurological assessment
  • Repeat B12, MMA, and homocysteine levels
  • Complete blood count normalization 1

Early diagnosis and prompt treatment are essential to prevent irreversible neurological damage in infants with vitamin B12 deficiency.