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Key Features

  • Caused by deficiency of cobalamin (vitamin B12), folic acid, or both

  • Cobalamin deficiency due to dietary insufficiency may occur in infants who are breast fed by mothers who are strict vegetarians or who have pernicious anemia

  • Intestinal malabsorption is the usual cause of cobalamin deficiency in children and occurs with

    • Crohn disease

    • Chronic pancreatitis

    • Bacterial overgrowth of the small bowel

    • Infection with the fish tapeworm (Diphyllobothrium latum)

    • After surgical resection of the terminal ileum

  • Deficiencies due to inborn errors of metabolism (transcobalamin II deficiency and methylmalonic aciduria) also have been described

  • Folic acid deficiency may be caused by inadequate dietary intake, malabsorption, increased folate requirements, or some combination of the three

Clinical Findings

  • Pallor and mild jaundice as a result of ineffective erythropoiesis

  • Classically, the tongue is smooth and beefy red

  • Infants with cobalamin deficiency may be irritable and may be poor feeders

  • Older children with cobalamin deficiency

    • May complain of paresthesias, weakness, or an unsteady gait

    • May show decreased vibratory sensation and proprioception on neurologic examination


  • Elevated mean corpuscular volume and mean corpuscular hemoglobin

  • Peripheral blood smear shows numerous macro-ovalocytes with anisocytosis and poikilocytosis

  • Neutrophils are large and have hypersegmented nuclei

  • The white cell and platelet counts are normal with mild deficiencies but may be decreased in more severe cases

  • Serum indirect bilirubin concentration may be slightly elevated

  • Low serum vitamin B12 level seen in cobalamin deficiency; may also be seen in about 30% of patients with folic acid deficiency

  • Elevated serum levels of metabolic intermediates (methylmalonic acid and homocysteine) may help establish the correct diagnosis


  • Cobalamin deficiency due to inadequate dietary intake is treated with high-dose oral supplementation that is as effective as parenteral treatment if absorption is normal

  • Folic acid deficiency is treated effectively with oral folic acid in most cases

  • Children at risk for the development of folic acid deficiencies, such as premature infants and those with chronic hemolysis, are often given folic acid prophylactically

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