Differentiation between Vitamin B12—deficient and Folic Acid—deficient Megaloblastic Anemias with C14—Histidine

Abstract

Abstract Intermediary metabolism of the monocarbon pool and histidine in normal subjects and patients with megaloblastic anemia was studied by continuous measurement of pulmonary excretion of C14O2 and urinary excretion of C14 after injection of L-histidine-2(ring)-C14. Cumulative pulmonary and renal excretion of C14 for 1 month by two normal subjects approximates 45 per cent of the amount injected. Within 4 months after injection of the dose used in this study, the resultant average tissue radiation decreases below the average natural terrestrial and cosmic radiation level. Simultaneous determination of two parameters, (1) cumulative 1-hour pulmonary C14 excretion and (2) the time of occurrence of maximum C14O2specific activity (Tmax), may permit rapid and unequivocal differentiation between folic acid deficiency and vitamin B12 deficiency in the pathogenesis of megaloblastic anemia. Folio acid deficiency results in marked diminution of pulmonary C14 excretion (approximately 0.1 per cent of injection C14 in 1 hour) and marked prolongation of C14O2-specific activity Tmax (approximately 3 hours), while both parameters are normal (approximately 1 per cent and less than 1 hour, respectively) in patients with vitamin B12 deficiency and megaloblastic anemia. Measurement during periods of reticulocyte response to either folio acid or vitamin B12 demonstrate normal C14O2-specific activity Tmax but decreased pulmonary C14 excretion. These observations suggest that prolongation of C14O2-specific activity Tmax is a sensitive index of folic acid deficiency or block and that if Tmax is normal, pulmonary C14 excretion is a sensitive index of the relative partition of the active monocarbon pool between pathways for oxidation and pathways for nucleic acid synthesis. This type of breath analysis seems to provide a quantitative dynamic representation of metabolic function which may be particularly useful in differentiating between the alterations of intermediary metabolism that occur in patients with folic acid-deficient megaloblastic anemia and in patients with vitamin B12-deficient megaloblastic anemia.