formiminoglutamic-acid and Anemia--Megaloblastic

Topics: Anemia, Megaloblastic; Animals; Female; Folic Acid; Folic Acid Deficiency; Formiminoglutamic Acid; Humans; Infant; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Male; Nutritional Requirements; Pregnancy; Pregnancy Complications, Hematologic; Vitamin B 12; Vitamin B 12 Deficiency

Women who use oral contraceptives have impaired folate metabolism as shown by slightly but significantly lower levels of folate in the serum and the erythrocytes and an increased urinary excretion of formiminoglutamic acid. The vitamin B12 level in their serum is also significantly lower than that of control groups. However, there is no evidence of tissue depletion of vitamin B12 associated with the use of oral contraceptives. The causes and clinical significance of the impairment of folate and vitamin B12 metabolism in these women is discussed in this review of the literature. Clinicians are advised to ensure that women who shop taking "the pill" because they wish to conceive have adequate folate stores before becoming pregnant.. The effects of oral contraception (OC) on folate and vitamin B12 metabolism are a subject of much controversy. Many studies indicate that OCs impair folate metabolsim and produce some degree of folate depletion, as demonstrated by slight but significant lower levels of folate in the serum and the erythrocytes, and by an increased urinary excretion of formiminoglutamic acid. These effects are unlikely to cause anemia or megalobastic changes in women who have a good dietary intake of folate. Since pregnant women are predisposed to the development of folate deficiency, it would be necessary when stopping the pill for desire of pregnancy to take folate supplements before becoming pregnant. OCs may also produce a low serum level of vitamin B12; this effect, however, is not associated with evidence of tissue depletion of vitamin B12, and does not have any great clinical significance; the effect may also be caused by vitamin B12 malabsorption rather than by OC treatment.

Topics: Anemia, Megaloblastic; Contraceptives, Oral; Erythrocyte Indices; Female; Folic Acid; Folic Acid Deficiency; Formiminoglutamic Acid; Hematocrit; Hemoglobins; Humans; Pregnancy; Vitamin B 12

Topics: Adult; Aged; Anemia, Megaloblastic; Anticonvulsants; Blood-Brain Barrier; Brain; Brain Diseases; Child; Epilepsy; Erythrocytes; Female; Folic Acid; Folic Acid Deficiency; Formiminoglutamic Acid; Humans; Intellectual Disability; Male; Mental Disorders; Metabolism, Inborn Errors; Methotrexate; Middle Aged; Nervous System Diseases; Vitamin B 12; Vitamin B 12 Deficiency

The diagnosis of megaloblastic anaemias caused by cobalamine or folate deficiency are still difficult. The dosage of these two substances help to differenciate between both carencies, but it is not determinant of any of them and is an expensive method. Homocisteinuria (HC), methylmalonuria (MMA) and formiminoglutamic acid (FIGLU) are cheap tests which could help in the differential diagnosis, if they are used properly. We report 62 patients to whom we made these test simultaneously. All of the patients received 10 micrograms of vit B12 and after 72 hours, 1 mg/day of folic acid (for 3 days). In both cases waiting for the increase of reticulocytyes up to 150 x 10(9)/L as a form of therapeutic test of diagnosis. By this simple way we have detected 97.9% of specificity for cobalamin deficiency of the MMA test, and only 4.2% for HC. This last test had increased its specificity up to 91.6% in association with the negative FIGLU test. We have also found a high specificity (92.3%) for FIGLU due to the detection of folate deficiency, in opposition with other authors who had described it as low as 50%. We have also compared the costs of the 3 tests with the dosage of cobalamine and folate, and we have found that the formers are 11 times less expensive than the last ones.

Topics: Adolescent; Adult; Algorithms; Anemia, Megaloblastic; Cost Control; Diagnosis, Differential; Diagnostic Tests, Routine; Female; Folic Acid; Folic Acid Deficiency; Formiminoglutamic Acid; Histidine; Homocysteine; Humans; Male; Methylmalonic Acid; Middle Aged; Predictive Value of Tests; Pregnancy; Pregnancy Complications, Hematologic; Reticulocyte Count; Retrospective Studies; Sensitivity and Specificity; Time Factors; Urinalysis; Vitamin B 12; Vitamin B 12 Deficiency

Megaloblastic anaemia is due to a derangement of DNA synthesis caused by insufficient supply of one or other of the four deoxyribonucleoside triphosphate (dNTP) precursors of DNA synthesis or by direct inhibition of one or other DNA polymerase. Reduced supply of the pyrimidine deoxythymidine triphosphate (dTTP) may be caused by folate or vitamin B12 deficiencies or by the action of dihydrofolate reductase inhibitors (e.g. methotrexate, pyrimethamine or trimethoprim), all of which cause reduced supply of the coenzyme 5, 10 methylene tetrahydrofolate (pentaglutamate) needed for thymidylate synthetase. Reduced dTTP supply may also be caused by direct inhibition of thymidylate synthetase by 5-fluorouracil. Reduced supply of both purines, deoxyadenosine triphosphate (dATP) and deoxyguanosine triphosphate (dGTP), may be caused by hydroxyurea, 6-mercaptopurine (and probably by another purine antagonist azaserine), whilst reduced supply of both pyrimidine DNA precursors, dTTP and dCTP (deoxycytidine triphosphate) may be due to inherited orotic aciduria or to treatment with azauridine. Cytosine arabinoside directly inhibits DNA polymerase. DNA replication is a discontinuous process and a number of enzymes are concerned with different aspects of the process. The parental strands partly unwind and a large number of initiation points or origins are activated on both strands. A primer RNA is first synthesised using the parental strand of DNA as template. Fragments of new DNA are then synthesised on the parental DNA template, starting at the RNA primer, under the action of one or other DNA polymerase (probably gamma). The RNA primer is then removed and the gap left is filled by further DNA synthesis under the action of a different DNA polymerase (probably alpha). The fragments of new DNA are joined to give newly synthesised stretches of DNA (replicons) which are then liigated together to form bulk DNA of enormous molecular weight. It is suggested here that reduced supply of one or other of the four deoxyribonucleoside triphosphate (dNTP) during the 'S' phase of the cell cycle (due to vitamin B12 or folate deficiency, drug treatment or other congenital or acquired abnormality in synthesis of the dNTP) impairs the cell's ability to elongate newly initiated DNA fragments by preventing gap-filling, the polymerase needed for gap-filling requiring substantially greater concentrations of the deoxyribonucleoside triphosphates than the polymerase involved in chain initiation. C

Topics: Anemia, Megaloblastic; DNA; Folic Acid; Folic Acid Deficiency; Formiminoglutamic Acid; Glycine; Homocysteine; Humans; Methionine; Methylmalonyl-CoA Mutase; Nervous System Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Megaloblastic; Female; Formiminoglutamic Acid; Glutamine; Histidine; Humans; Pregnancy; Pregnancy Complications

Topics: Anemia; Anemia, Aplastic; Anemia, Hemolytic; Anemia, Megaloblastic; Ankyrins; Formiminoglutamic Acid; Glutamates; Hematopoiesis; Humans; Imidazoles; Jaundice; Medical Records; Spherocytosis, Hereditary; Urocanic Acid

Topics: Anemia; Anemia, Macrocytic; Anemia, Megaloblastic; Deficiency Diseases; Female; Folic Acid; Formiminoglutamic Acid; Glutamates; Malnutrition; Pregnancy; Pregnancy Complications