Megaloblastic anaemia, cobalamin, and folate.
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Developments relating to cobalamin and folate are reviewed. Current work on the relations between these two coenzymes are discussed, particularly those that have emerged in studies using nitrous oxide, which inactivates cobalamin. (+info)
Genetic heterogeneity among patients with methylcobalamin deficiency. Definition of two complementation groups, cblE and cblG.
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A number of patients with megaloblastic anemia and homocystinuria associated with low levels of methylcobalamin synthesis in cultured cells have been recognized. Methionine biosynthesis by intact cells, as determined by incorporation of label from 5-[14C]methyl-tetrahydrofolate into acid-precipitable material, was deficient in cultured skin fibroblasts that were derived from all of these patients. In one group of patients, activity of the methylcobalamin-dependent enzyme, methionine synthase, in cell extracts was within the normal range when the enzyme was assayed under standard conditions. In a second group of patients, methionine synthase activity was decreased under the same assay conditions. Genetic complementation analysis demonstrated the existence of two complementation classes that corresponded to these two groups of patients. The designation cblE has previously been proposed for normal methionine synthase activity. We propose the designation cblG for the mutation in those patients with methylcobalamin deficiency and decreased synthase activity. The results of these studies suggest that the products of at least two loci are required for cobalamin-dependent methionine biosynthesis in mammalian cells. (+info)
Diagnostic and prognostic value of DNA image cytometry in myelodysplasia.
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The DNA content of erythropoietic cells from 10 patients with refractory anaemia (RA) with megaloblastic changes, who subsequently developed acute non-lymphoblastic leukaemia (ANL), and from seven patients with megaloblastic marrow aspirates due to pernicious anaemia were compared by DNA image cytometry. The DNA distribution, the rate of aneuploid cells exceeding 5c (5cER), and the square deviation index of DNA values from the normal 2c-peak (2cDI) were recorded. Both variables were of diagnostic and prognostic importance for epithelial tumours, malignant lymphomas, and dysplastic lesions. A rate of 5cER greater than 0 was found in eight of 10 myelodysplastic, but in none of seven control cases. Hypodiploidy was equally pronounced in both groups of patients. The 5cE had the highest discriminative value of all variables calculated. The 2cDI was not significantly different in either group. In pernicious anaemia the 2cDI depended mainly on the percentage of S cells, reflecting the defect of DNA synthesis. In RA with megaloblastosis the 2cDI correlated with the percentage of G2 cells, reflecting G2 arrest. In the myelodysplastic group the 2cDI correlated positively with the length of time until ANL developed, indicating the prognostic relevance of 2cDI. Our findings show that in megaloblastic anaemia DNA image cytometry can distinguish myelodysplasia from pernicious anaemia and that it also provides prognostic information. (+info)
The intestinal absorption of folates.
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Dietary folates, existing primarily in the form of pteorylpolyglutamates, are absorbed in the jejunum by a process involving hydrolysis and subsequent intestinal transport of pterolymonoglutamyl folate. Current evidence indicates that one (or more) intestinal mucsoal enzyme(s), termed folate conjugase, is required for the hydrolysis of pteroylpolyglutamate to pteroylmonoglutamyl folate. Unresolved controversies include the mucosal location of hydrolysis (surface versus intracellular), whether the transport of pteroylmonoglutamate is active or passive, and the relation of intestinal mucosal metabolism of pteroylmonoglutamate to its intestinal transport. (+info)
The laboratory diagnosis of megaloblastic anemias.
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The diagnostic approach to megaloblastic anemia involves four usually sequential steps. The first step, recognition of megaloblastosis, requires attention to altered blood cell size and morphology. These changes may sometimes be subtle or masked. The cornerstone of the second step, identification of the specific vitamin deficiency, is assay of serum vitamin B(12) and folic acid levels, although they may occasionally be misleading. The third step, identification of the specific disease entity responsible for the vitamin deficiency, generally revolves around tests of absorption and gastric function. The fourth step, reevaluation after replacement therapy, is often not thought of as a diagnostic step but carries important diagnostic implications and is sometimes the only way in which coexisting abnormalities can be unmasked and identified. (+info)
Laboratory diagnosis of megaloblastic anaemia: current methods assessed by external quality assurance trials.
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The results of an Interregional quality assurance scheme for tests in the diagnosis of megaloblastic anaemia were reviewed to assess the methods used. Serum folate assays showed great variation between methods, partly due to limitations in assessment by external quality assurance. Red cell folate assays yielded widely different results and much imprecision due both to the differences in preparation of the haemolysate and to the problems inherent in radioassay of a mixture of folate compounds. Intrinsic factor antibody tests showed appreciable variation in sensitivity. There was considerable inconsistency in the detection of polymorph nuclear hypersegmentation. (+info)
Methionine partially corrects the impaired deoxyribonucleic acid synthesis of B12-deficient megaloblastic bone marrow cells at low concentration.
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The effects of methionine on deoxyribonucleic acid (DNA) synthesis of B12-deficient megaloblastic bone marrow cells were investigated over a wide concentration range. Deoxyuridine (UdR) incorporation and the UdR suppression test were employed as an indicator for DNA synthesis. Only a low and limited concentration range of methionine improved significantly the impaired DNA synthesis of megaloblastic cells, although the extent of improvement was less than those by either B12 or folate. Higher concentrations of methionine (greater than or equal to 150 micrograms/ml), however, were suppressive for both megaloblastic and normoblastic cells. In contrast, homocysteine did not affect DNA synthesis of megaloblastic cells at low concentration. Improving effect of methionine at low concentration appeared to be characteristic to megaloblastic cells, since such effect disappeared on hematologic recovery following B12 administration. (+info)
We report a case of congenital isolated malabsorption of folic acid, the first in a boy. Only seven previous cases have been reported, and we discuss two aspects--namely, the tendency to infection, with evidence of impairment of both cellular and humoral immunity, and the absence of neurological disturbances. (+info)