Impairment of Nuclear Development Due to Lack of B12 or Folate

The cause of impaired nuclear development in megaloblastic anemia is either an impairment or lack of vitamin B12 or folate utilization. Both vitamins are essential for DNA synthesis and work within the same cycle. Thus, if either is deficient, the cycle will not continue and DNA synthesis will be impaired. The development of the nucleus will lag behind cytoplasmic development, a situation known as asynchronous maturation. Additionally, the abnormal precursor cells may die through apoptosis leading to anemia.

Please see the B12/folate metabolic cycle to the right. To explain: vitamin B12 is necessary to drive the folate cycle, which is important in converting uridylates to thymidylates, which are necessary for the production of the nucleic acid thymidine, which is necessary for DNA synthesis.

One important fact to keep in mind: Not all patients who have B12 or folate deficiencies will necessarily exhibit macrocytosis. It is possible that the patient could also have a concomitant iron deficiency. Iron-deficient erythropoiesis, which typically produces microcytic cells, can mask macrocytosis. More about this under laboratory diagnosis and testing.