Anemias folate deficiency causing

Be aware of how folate deficiency causes megaloblastic anemia. 

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... 

Pernicious anemia arises when vitamin B,2 deficiency blocks the metabohsm of folic acid, leading to functional folate deficiency. This impairs erythropoiesis, causing immature precursors of erythrocytes to be released into the circulation (megaloblastic anemia). The commonest cause of pernicious anemia is failure of the absorption of vitamin B,2 rather than dietary deficiency. This can be due to failure of intrinsic factor secretion caused by autoimmune disease of parietal cells or to generation of anti-intrinsic factor antibodies. 

Vitamin deficiency can cause a megaloblastic anemia of the same type seen in folate deficiency (discussed in Chapter 17). In a patient with megaloblastic anemia, it is important to determine the underlying cause because Bjj defidency, if not corrected, produces a peripheral neuropathy owing to aberrant fatty acid incorporation into the myelin sheets associated with inadequate methylmalonyl CoA mutase activity. Excretion of methylmalonic acid indicates a vitamin Bjj deficiency rather than folate. 

Answen B. Methyhnalonyl CoA mutase requires Bj but not folate for activity. Macrocytic anemia, elevated homocysteine, and macrocytic anemia can be caused by either B,2 or folate deficiency. 

Flypersensitivity to TMP or SMZ megaloblastic anemia caused by folate deficiency ... 

Reduced forms of folic acid are required for essential biochemical reactions that provide precursors for the synthesis of amino acids, purines, and DNA. Folate deficiency is not uncommon, even though the deficiency is easily corrected by administration of folic acid. The consequences of folate deficiency go beyond the problem of anemia because folate deficiency is implicated as a cause of congenital malformations in newborns and may play a role in vascular disease (see Folic Acid Supplementation A Public Health Dilemma). 

Folate deficiency results in a megaloblastic anemia that is microscopically indistinguishable from the anemia caused by vitamin B12 deficiency (see above). However, folate deficiency does not cause the characteristic neurologic syndrome seen in vitamin B12 deficiency. In patients with megaloblastic anemia, folate status is assessed with assays for serum... 

Folic acid deficiency can be caused by drugs. Methotrexate and, to a lesser extent, trimethoprim and pyrimethamine, inhibit dihydrofolate reductase and may result in a deficiency of folate cofactors and ultimately in megaloblastic anemia. Long-term therapy with phenytoin can also cause folate deficiency, but only rarely causes megaloblastic anemia. 

Methylmalonyl CoA mutase is especially sensitive to vitamin B12 depletion, so methylmalonic aciduria is the most sensitive index of vitamin B12 status. Folate deficiency does not cause methylmalonic aciduria. However, up to 25% of patients with confirmed pernicious anemia excrete normal amounts of methylmalonic acid, even after a loading dose of valine (Chanarin et al., 1973). 

DEFICIENCY Folate deficiency resembles B12 deficiency so far as the anemia goes, but without the neurologic abnormalities. Unlike B12, for which there are tremendous body stores, folate needs continued replacement, and poor diet is the most common cause of folate deficiency. Serum levels of folate may help establish the diagnosis. Pregnant women are encouraged to take folate in pregnancy to help prevent birth defects. 

The major cause of megaloblastic anemia in children is folate deficiency. The following case indicates the importance of including regular supplementation of parenteral nutrition with folate (74). 

Triamterene blocks dihydrofolate reductase and can cause folate deficiency with megaloblastic anemia and pancytopenia, particularly in patients with hepatic cirrhosis, who have reduced clearance of the drug (SED-11, 431). When this has been reported, all patients were taking doses of 150-600 mg/day for ascites and all had hepatic cirrhosis, often due to alcohol abuse (SEDA-17, 269). It is advisable to use spironolactone rather than triamterene in patients with cirrhosis. 

A. Pernicious anemia occurs when the stomach does not produce adequate intrinsic factor for absorption of vitamin B12, which is required for the conversion of methylmalonyl CoA to succinyl CoA and homocysteine to methionine. A vitamin B12 deficiency results in the excretion of methylmalonic acid and an increased dietary requirement for methionine. The methyl group transferred from vitamin B12 to homocysteine to form methionine comes from 5 -methyl tetrahydrofolate, which accumulates in a vitamin B12 deficiency, causing a decrease in folate levels and symptoms of folate deficiency, including increased levels of FIGLU and decreased purine biosynthesis. 

A CBC, including a peripheral smear and reticulocyte count, should be performed in any elderly patient with symptoms that may be attributed to anemia, along with a physical exam to look for signs of renal or hepatic failure as well as to evaluate for gastrointestinal or genitourinary blood loss. If the reticulocyte count is adequate, blood loss or RBC destruction should be suspected, whereas a low level will indicate decreased RBC production. With a low reticulocyte count, RBC indices should be evaluated and if the MCV is > 100 fL, further evaluation should be performed to discern vitamin B12 deficiency and folate deficiency as possible causes. A vitamin B12 deficiency may be present even when plasma levels of vitamin B12 are within normal range, but elevated levels of MMA will detect the deficiency. A refractory macrocytic anemia in the elderly should raise suspicion of a myelodysplastic or leukemic syndrome. 

B. Megaloblastic anemia is caused by a decrease in the synthesis of deoxythymidylate and the purine bases usually caused by a deficiency in either THF or cobalamin or both. This results in decreased DNA synthesis, which results in abnormally large hematopoietic cells created by perturbed cell division and DNA replication and repair. This patient exhibits signs of chronic alcoholism, which often leads to a folate deficiency. This can occur due to poor dietary intake, decreased absorption of folate due to damage of the intestinal brush border cells and resulting conjugase deficiency, and poor renal resorption of folate. 

Causes of megaloblastic anemia Folate and cobalamin deficiency. Patients with folate deficiency have similar hematologic and GI findings but do not have the neurologic symptoms as with cobalamin deficiency. 

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