Dr Ira Shah,Dr.
MD, DCH (Gold Medalist), FCPS, DNB

Kalpana Sengupta

A 7 month old female child born of third degree consanguineous marriage presented with high grade fever since 8 days and bruise on back since 4 days. She had a history of LRTI 1 month back for which she was treated with IV antibiotics. She was a full term normal vaginal delivery with a birth weight of 2.25 kg. She was exclusively breast fed with both the parents being vegetarian. On examination, she had tachycardia (heart rate =140/minute), pallor and multiple petechiae over the abdomen, legs and trunk. There was a bruise present over the lower back (3cm x 2cm). She had hyperpigmented nail folds. There was no jaundice, lymphadenopathy or bone tenderness. She had hepatosplenomegaly.

Thus, the clinical impression was hepatosplenomegaly with pancytopenia (in view of fever, petechiae and pallor) with CCF to rule out megaloblastic anemia (dietary deficiency) or leukemia.

Her investigations showed Hb of 4.5 gm/dl, WBC count of 6,100/cumm (ANC=976/cumm) and platelet count of 32,000/cumm suggestive of pancytopenia. Peripheral smear was suggestive of hypopolychromasia, Howell Jolly bodies, poikilocytosis with presence of macrocytes and basophilic stippling. Platelets were decreased on smear. Her MCV was 100 fl (Normal= 95 fl), MCH = 39.3 pg (Normal = 24 -34 pg) and MCHC= 39% (Normal=32-35%). Her reticulocyte count was 2% with a corrected reticulocyte count being 0.5%.

In view of the low reticulocyte count, a bone marrow aspiration was done which showed presence of megaloblasts. Her serum was highly lipemic with S.LDH being 4177 IU/ml (Normal = 52 – 149 IU/ml). Hence a diagnosis of megaloblastic anemia was established. Her Serum B12 and folic acid levels could not be done due to non-affordability.

She was treated with Inj Vitamin B12 (1mg IM) and folic Acid (5mg daily). She also required 2 blood transfusions in view of her CCF. After 7 days of treatment and following blood transfusion, her Hb was 11.1 gm/dl, MCV= 94.5 fl, MCH=31 pg and MCHC= 32.9%. The platelet count was 1,31,000/cumm and there was a reticulocyte response with reticulocytes being 10.5%. Her ANC rose to 4100/ cumm. She was also supplemented with iron to prevent iron deficiency in view of increased cell turnover and weaning was advised. Her mother was also started on Vitamin B12 and folic acid supplementation.

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.

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.