Megaloblastic anemia results from deficiency of folic acid or Vitamin B12 or both. Both Vitamin B12 and folic acid are required in the synthesis of nucleoproteins and deficiency results in defective synthesis of DNA & RNA. Ineffective erythropoiesis results due to arrest or premature death of cells in the marrow. In the peripheral smear, the red blood cells are large (macrocytosis) and hypersegmented neutrophils are present. In the marrow megaloblasts are seen.

Folic acid deficiency : It is seen in infants between 4-7 months of age and is associated usually with a diet deficient in folic acid. (Folates are present in green vegetables, fruits, liver and kidney). Goat milk is deficient in folic acid. Patients with folic acid deficiency have anemia, irritability, failure to gain weight adequately and chronic diarrhea. Hemorrhages due to thrombocytopenia may occur. RBC folate levels are decreased. (Normal RBC folate level= 150 to 600 ng/ml of packed cells). Serum LDH is markedly elevated and megaloblastic changes occur in the bone marrow Treatment consists of folic acid supplementation in the dose of 1-5mg/day for 3-4 Weeks.

Figure 1: Sequence of appearance of abnormalities in the blood & bone marrow due to dietary folate deficiency

Vitamin B12 deficiency: Vitamin B12 is derived from cobalamin in food mainly animal sources. An exclusive vegetarian diet contains no vitamin B12. Vitamin B12 deficiency may occur due to poor dietary intake, exclusive breast feeding in infants with maternal deficiency, defective absorption due to lack of intrinsic factor (pernicious anemia) or generalized deficiency of transcobalamin II. A child with Vitamin B12 deficiency presents similar to that of folic acid deficiency. Neurologic signs such as ataxia, paraesthesia, hyporeflexia, clonus may be present. In addition to macrocytes, in advanced cases, neutropenia and thrombocytopenia may occur. Serum B12 levels are less than 100 pg/ml Excessive excretion of methylmalonic acid in urine may occur. Once B12 deficiency has been identified an attempt should be made to identify the pathogenesis. This may include a careful dietary history, an upper Gl series, Schilling test (to assess absorption of Vitamin B12 and deficiency of intrinsic factor), assay of gastric acidity, determination of antibodies to parietal cells & extrinsic factors and gastric biopsy. Treatment consists of vitamin B12 (1mg) parenteral, which is followed by reticulocytosis in 2-4 days. If there is evidence of neurological involvement, 1mg should be injected IM daily for 2 weeks atleast followed by maintenance recommended allowance. In case of intrinsic factor deficiency, IM administration of 1mg of B12 is required monthly for the lifetime.