Anemia, Megaloblastic

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

Diagnosis

• 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

Treatment

• 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