Megaloblastic anemia diagnosis

Fohc acid is a precursor of several important enzyme cofactors required for the synthesis of nucleic acids (qv) and the metaboHsm of certain amino acids. Fohc acid deficiency results in an inabiUty to produce deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and certain proteins (qv). Megaloblastic anemia is a common symptom of folate deficiency owing to rapid red blood cell turnover and the high metaboHc requirement of hematopoietic tissue. One of the clinical signs of acute folate deficiency includes a red and painhil tongue. Vitamin B 2 folate share a common metaboHc pathway, the methionine synthase reaction. Therefore a differential diagnosis is required to measure foHc acid deficiency because both foHc acid and vitamin B 2 deficiency cause... 

The fibroblasts do not convert cyanocobalamin or hydroxocobalamin to methylcobalamin or adenosyl-cobalamin, resulting in diminished activity of both N5-methyltetrahydrofolate homocysteine methyltransferase and methylmalonyl-CoA mutase. Supplementation with hydroxocobalamin rectifies the aberrant biochemistry. The precise nature of the underlying defect remains obscure. Diagnosis should be suspected in a child with homocystinuria, methylmalonic aciduria, megaloblastic anemia, hypomethioninemia and normal blood levels of folate and vitamin B12. A definitive diagnosis requires demonstration of these abnormalities in fibroblasts. Prenatal diagnosis is possible. 

The answer is D. Several vitamin deficiencies can cause anemia due to reduced DNA synthesis in the erythropoietic cells of the bone marrow, especially folic acid and vitamin Bj2 (cobalamin), which are particularly prevalent among elderly patients due to poor diet and reduced absorption. In addition, deficiencies of either folic acid or vitamin Bj2 could produce the megaloblastic anemia seen in this patient. However, the absence of neurologic symptoms, a hallmark of vitamin Bj2 deficiency, makes that diagnosis less likely than folic acid deficiency. 

Without a firm diagnosis folic acid should not be given to all patients with megaloblastic anemia as irreversible neurological damage from vitamin B12... 

Once a diagnosis of megaloblastic anemia is made, it must be determined whether vitamin B12 or folic acid deficiency is the cause. (Other causes of megaloblastic anemia are very rare.) This can usually be accomplished by measuring serum levels of the vitamins. The Schilling test, which measures absorption and urinary excretion of radioactively labeled vitamin B12, can be used to further define the mechanism of vitamin Bi2 malabsorption when this is found to be the cause of the megaloblastic anemia. 

E. The correct diagnosis is thalassemia minor because the patient had been asymptomatic until age 7 years. If he had thalassemia major or Cooley anemia, he would have exhibited symptoms as early as his first birthday. Pernicious anemia leads to a macrocytic or megaloblastic anemia, whereas aplastic anemia is characterized by normal sized erythrocytes. 

Folic deficiency was thought to be rare in humans, but more and more cases of deficiency were reported as the methods for diagnosis improved. It is now sometimes assumed to be one of the most common vitamin deficiencies. In humans, megaloblastic anemia develops after five months of administration of a folic acid-deficient diet, suggesting that it takes that long to deplete the body of its folic acid reserves or sources. The exact human requirements for folic acid are unknown, but it is estimated that 50-250 pg of folic acid is required daily in adults and 5-20 pg in infants. These figures are based on the hematological response observed in patients with folic acid deficiency. 

In tropical megaloblastic anemias, whether associated with pregnancy or not, dietary deficiency is the rule and free hydrochloric acid is usually present in the gastric juice. Diarrhea is not infrequent and sometimes leads to a diagnosis of tropical sprue, although the latter is a quite distinct condition. 

Relapsing megaloblastic anemia in a girl aged six years responded to vitamin B12, but free hydrochloric acid was present in the gastric juice, and occult steatorrhea was not excluded (Davis et cd., 1949). Even persistent achlorhydria, absence of steatorrhea, and a response to vitamin Bu do not permit a diagnosis of Addisonian pernicious anemia to be made with certainty. 

---