Definitions

hypovitaminosis

Megaloblastic anemia

Megaloblastic anemia is an anemia (of macrocytic classification) which results from inhibition of DNA synthesis in red blood cell production. This is often due to deficiency of vitamin B and/or folic acid. Megaloblastic anemia not due to hypovitaminosis may be caused by antimetabolites which poison DNA production, such as some chemotherapeutic agents.

It is characterized by many large immature and dysfunctional red blood cells (megaloblasts) in the bone marrow, and also by hypersegmented or multisegmented neutrophils.

Causes

Hematological findings

The blood film can point towards vitamin deficiency:


Blood chemistries will also show:

  • Increased homocysteine and methylmalonic acid in B deficiency
  • Increased homocysteine in folate defiency

Normal levels of both methylmalonic acid and total homocysteine rule out clinically significant cobalamin deficiency with virtual certainty.


Bone marrow (not normally checked in a patient suspected of megaloblastic anemia) shows megaloblastic hyperplasia.

Analysis

The gold standard for the diagnosis of B deficiency is a low blood level of B. A low level of blood B is a symptom which normally can and should be treated by injections, supplementation, or dietary or lifestyle advice, but it is not a diagnosis. Hypovitaminosis B can result from a number of mechanisms, including those listed above. For determination of etiology, further patient history, testing, and empirical therapy may be clinically indicated. A measurement of methylmalonic acid can provide an indirect method for partially differentiating B12 and folate deficiencies. The level of methylmalonic acid is not elevated in folic acid deficiency. But direct measurement of blood cobalamin remains the gold standard because the test for elevated methylmalonic acid is not specific enough. Vitamin B is one necessary prosthetic group to the enzyme methylmalonyl-coenzyme A mutase. B deficiency is but one among the conditions that can lead to dysfunction of this enzyme and a buildup of its substrate, methylmalonic acid, the elevated level of which can be detected in the urine and blood.

Due to the lack of available radioactive B, the Shilling test is now largely a historical artifact. The Schilling test was performed in the past to help determine the nature of the vitamin B deficiency. An advantage of the Shilling test was that it often included B with intrinsic factor.

References

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