Causes of Vitamin B12 Deficiency in Children
Vitamin B12 deficiency in children primarily results from maternal deficiency transmitted through breastfeeding, malabsorption disorders, and inadequate dietary intake, with exclusively breastfed infants of deficient mothers representing the most common and preventable cause.
Maternal-Related Causes
Maternal Dietary Deficiency
- Vegetarian and vegan maternal diets are the leading cause of infant B12 deficiency, as vitamin B12 is found exclusively in animal foods (meat, fish, poultry, cheese, milk, eggs) 1.
- Exclusively breastfed infants develop deficiency between 2-12 months of age when maternal stores are inadequate 2, 3.
- Infants born to deficient mothers have low hepatic B12 storage at birth, making them vulnerable even when mothers are asymptomatic 3.
Maternal Malabsorption Conditions
- Maternal pernicious anemia (autoimmune destruction of intrinsic factor) causes infant deficiency through inadequate breast milk B12 content 4.
- Maternal gastrectomy eliminates intrinsic factor production, leading to severe maternal and subsequent infant deficiency 5.
- Maternal atrophic gastritis affecting the gastric body impairs B12 absorption and can affect breastfed infants 6.
Gastrointestinal Causes in Children
Surgical Causes
- Distal ileum resection >20 cm causes permanent B12 malabsorption requiring lifelong supplementation, as the terminal ileum is the sole absorption site 1, 6.
- Total or partial gastrectomy eliminates intrinsic factor production necessary for B12 absorption 7.
- Bariatric surgery reduces hydrochloric acid and intrinsic factor availability 6.
Malabsorption Disorders
- Celiac disease (gluten enteropathy) damages the small intestinal mucosa, impairing B12 absorption 1, 7.
- Small bowel bacterial overgrowth competes for available B12 before absorption 7.
- Fish tapeworm infestation (Diphyllobothrium latum) consumes dietary B12 7.
- Inflammatory bowel disease, particularly ileal Crohn's disease, damages the absorption site 6.
Autoimmune Conditions
- Pernicious anemia in children results from anti-intrinsic factor or anti-parietal cell antibodies preventing B12 absorption 4.
- Autoimmune gastritis progressively destroys gastric parietal cells 8.
Medication-Induced Deficiency
Multiple medications interfere with B12 absorption or utilization 6, 8:
- Metformin (especially >4 months use)
- Proton pump inhibitors and H2 receptor antagonists (>12 months use)
- Colchicine
- Anticonvulsants (phenobarbital, pregabalin, primidone)
- Sulfasalazine
- Methotrexate
Inadequate Intake
Dietary Insufficiency
- Strict vegetarian/vegan diets without supplementation provide no B12, as it occurs only in animal products 1, 7.
- Inadequate dietary intake in children with restricted diets or poor appetite 1.
Increased Requirements
- Pregnancy and lactation increase B12 requirements, potentially depleting maternal stores 7.
- Conditions causing increased demand: thyrotoxicosis, hemolytic anemia, hemorrhage, malignancy, hepatic and renal disease 7.
Special Populations at Risk
Infants on Parenteral Nutrition
- Long-term parenteral nutrition without adequate B12 supplementation (recommended 0.3 μg/kg/day for infants <12 months) 1.
Children with Chronic Kidney Disease
- Children on dialysis have decreased intake, increased clearance, and dialysis-related losses of water-soluble vitamins including B12 1.
Genetic/Metabolic Causes
- Congenital disorders of B12 metabolism including transcobalamin deficiency (TCN2 gene) and intracellular cobalamin metabolism defects (MMACHC, MMADHC, MTRR, MTR genes) 6.
- These present with elevated methylmalonic acid despite normal or elevated serum B12 6.
Critical Clinical Pitfalls
Never administer folic acid before treating B12 deficiency, as folic acid may mask anemia while allowing irreversible neurological damage to progress 6, 7. This is particularly dangerous as doses of folic acid >0.1 mg/day can produce hematologic remission in B12-deficient patients while neurologic manifestations continue unchecked 7.
Vitamin B12 deficiency allowed to progress >3 months produces permanent degenerative spinal cord lesions 7. Symptoms in infants include vomiting, lethargy, failure to thrive, hypotonia, developmental regression, and abnormal movements (tremors, myoclonus) appearing between 2-12 months of age 2.
Always obtain maternal nutritional history in breastfed infants presenting with developmental delay or neurological symptoms, specifically asking about vegetarian/vegan diets, gastrectomy, or autoimmune conditions 2, 3, 4.