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Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Folate absorption and transport were studied in young (2 to 3 months) and aged (28 to 30 months) rats. From studies of the rise in serum folate levels after ingestion and transport across everted intestinal segments it was concluded that the absorption of dietary polyglutamyl folates was impaired in aged animals. Simple folates (monoglutamyl pteroates) were utilized equally well in both age groups. Decreased hydrolysis of polyglutamylfolates to simple forms have been observed in the aged group. High folyl conjugase (pteroyl gamma-glutamyl hydrolase) levels are induced in pancreas as a response to dietary folate intake; the conjugase is secreted into the gut lumen where enzyme levels rise sequentially reaching maximum in the midgut region within 30 to 60 min after folate ingestion. The rise in serum folate after folate ingestion parallels the rise in luminal folyl conjugase. Pancreatic and luminal conjugases (but not mucosal conjugase) have similar pH optima. It is suggested that dietary folates are preferentially hydrolyzed to absorbable forms by a luminal folyl conjugase which is of pancreatic origin. The overall enzyme levels are much lower in pancreas of the aged rats, leading to reduced availability of absorbable dietary folates and resulting in folate malabsorption in these animals. It is suggested that the intestinal mucosal conjugase does not play a significant role in the physiological absorption of dietary folates.
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PMID:Folate malabsorption in aged rats related to low levels of pancreatic folyl conjugase. 621 50

The folic acid plasma level in 12 out of 13 children with thalassemia major was lower than 3 ng/ml. This deficiency is not due to intestinal malabsorption. Folate deficiency should then be provoked by an increased allowance due to the compensatory erythropoiesis and to the lack of. Folic acid level less then 3 ng/ml in 24% and not more then 6 ng/ml in 50% of thalassemic heterozygotic children has been found. Therefore the necessity of folic acid treatment in thalassemic children with a low blood transfusional therapy and in beta-thalassemic heterozygotic children has been recommended.
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PMID:[Behavior of blood folate in children with thalassemia major under transfusion therapy and in thalassemia trait]. 652 78

Congenital errors of folate metabolism can be related either to defective transport of folate through various cells or to defective intracellular utilization of folate due to some enzyme deficiencies. Defective transport of folate across the intestine and the blood-brain barrier was reported in the condition 'Congenital Malabsorption of Folate'. This disease is characterized by a severe megaloblastic anaemia of early appearance associated with mental retardation. Anaemia is folate-responsive, but neurological symptoms are only poorly improved because of the inability to maintain adequate levels of folate in the CSF. A familial defect of cellular uptake was described in a family with a high frequency of aplastic anaemia or leukaemia. An isolated defect in folate transport into CSF was identified in a patient suffering from a cerebellar syndrome and pyramidal tract dysfunction. Among enzyme deficiencies, some are well documented, others still putative. Methylenetetrahydrofolate reductase deficiency is the most common. The main clinical findings are neurological signs (mental retardation, seizures, rarely schizophrenic syndromes) or vascular disease, without any haematological abnormality. Low levels of folate in serum, red blood cells and CSF associated with homocystinuria are constant. Methionine synthase deficiency is characterized by a megaloblastic anaemia occurring early in life that is more or less folate-responsive and associated with mental retardation. Glutamate formiminotransferase-cyclodeaminase deficiency is responsible for massive excretion of formiminoglutamic acid but megaloblastic anaemia is not constant. The clinical findings are a more or less severe mental or physical retardation. Dihydrofolate reductase deficiency was reported in three children presenting with a megaloblastic anaemia a few days or weeks after birth, which responded to folinic acid. The possible relationship between congenital disorders such as neural tube defects or dihydropteridine reductase deficiency and disturbances of folate metabolism are discussed. Neurological symptoms present in most of these congenital disorders highlight the role of folate in the central nervous system.
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PMID:Congenital errors of folate metabolism. 853 63

Deficient activity of an enzyme can result from a defect in the conversion of the vitamin to a co-enzyme as well from an abnormal apo-enzyme or disturbed binding of coenzyme to enzyme. Conversion of dietary vitamin to intracellular active co-enzyme can be complex and require many physiological and biochemical processes including stomach release of bound vitamin, intestinal uptake, carriers/transport, blood transport, cellular uptake, intracellular release and intracellular compartmentalisation. Disorders of malabsorption (food cobalamin malabsorption, intrinsic factor deficiency and abnormal enterocyte cobalamin processing) and transport proteins (transcobalamin II deficiency, R-binder deficiency) mostly lead to disturbed function of the two cobalamin requiring enzymes, methylmalonyl CoA mutase and methionine synthase. Defects of early steps of intracellular cobalamin (cblF, cbl C/D) result in marked deficiencies of both cobalamin co-enzymes and homocystinuria combined with methylmalonic aciduria. Defective synthesis of adenosyl cobalamin in the cbl A/B defects leads to methylmalonyl CoA mutase. Isolated methionine synthase deficiency is also classified as a cobalamin disorder due to its associated deficient formation of methylcobalamin. Folate disorders include methylene-tetrahydrofolate reductase deficiency and glutamate formimino-transferase deficiency. In addition a hereditary disorder of intestinal folate transport has been described. Less well established are disorders of dihydrofolate reductase, methenyl-tetrahydrofolate cyclohydrolase, and defects of cellular folate uptake.
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PMID:Genetic defects of folate and cobalamin metabolism. 958 28

Several fundamental questions relating to the biochemical basis of megaloblastic hemopoiesis in vitamin B12 (B12) and folate deficiency and neurological damage in B12 deficiency remain to be answered. Among them is the explanation underlying (1) the failure of B12-deficient animals to develop megaloblastic hemopoiesis despite indirect evidence of impaired thymidylate synthesis and (2) the inverse relationship between the extent of hematologic and neurological damage in B12 deficiency. Diagnostic advances have led to the awareness that many patients with B12 or folate deficiency are hematologically normal and that subtle hematologic or neuropsychiatric manifestations may be found at a fairly early stage of developing B12 deficiency. Studies of the mechanism of absorption of B12 in food have identified the syndrome of food B12 malabsorption in which the degree of B12 deficiency is commonly, although not invariably, mild. Folate intake influences the prevalence of neural tube defects (NTDs) and a suboptimal folate status may be associated with an increased risk for dysplasia and cancer. The latter may be at least partly the result of uracil misincorporation into DNA and consequent DNA strand breaks. Folate status has also been linked to arteriosclerotic vascular disease through its effect on serum homocysteine levels. Uracil misincorporation into DNA and increased serum homocysteine levels may also be found in B12 deficiency. These adverse associations form the basis of a case for improving B12 or folate status in individuals with a mild degree of deficiency. Because inadequate folate intake is relatively common, especially in the elderly and the poor, the fortification of staple foods with folate is currently under active consideration.
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PMID:The wide spectrum and unresolved issues of megaloblastic anemia. 993 May 65

Folate or cobalamin deficiencies are usually detected by hematologic abnormalities, such as a macrocytic megaloblastic anemia, or often milder signs, such as hypersegmented neutrophils. In fact, these vitamin deficiencies may be associated with clinical conditions in which anemia and/or macrocytosis are absent, such as neuropsychiatric disorders and inborn errors of folate or cobalamin metabolism. A battery of sensitive tests, including blood vitamin levels, serum methylmaIonic acid and homocysteine assays, and the deoxyuridine suppression test in the bone marrow, allows for early detection of vitamin deficiency. Additional tests may be included to identify the causes of deficiency, such as the Schilling test using crystalline cyanocobalamin, or a modified Schilling test for showing food cobalamin malabsorption. Strategies for diagnosing a vitamin deficiency differ according to the hematologic and clinical presentations. The deleterious effects (aside from anemia) that arise from cobalamin or folate deficiency and include neurological complications, increased risk of vascular disease due to hyperhomocysteinemia, and increased risk of some types of cancer related to folate deficiency, underscore the importance of making an early diagnosis and instituting treatment with the appropriate vitamin in preventing permanent damage.
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PMID:Modern clinical testing strategies in cobalamin and folate deficiency. 993 May 67

Folate plays a key role in nucleic acid synthesis. As a consequence, the most conspicuous complication of folate deficiency or of derangements of folate metabolism is megaloblastic macrocytic anemia caused by interdiction of normal proliferation of rapidly dividing bone marrow cells. Other rapidly dividing cells, including those in the gastrointestinal tract, may also be affected by the megaloblastic process. This may result in malabsorption. However, there is mounting evidence to indicate that there are other earlier manifestations of folate deficiency or of longstanding suboptimal folate nutrition. Chief among these manifestations of folate deficiency are an increased predisposition to occlusive vascular disease and thrombosis, which have been linked to increased levels of homocysteine found in folate deficiency and abnormal states of folate metabolism. In addition, folate deficiency, previously considered free of neurological consequences, is now known to be associated with disturbances of mood, and even spinal cord syndromes similar to those seen in vitamin B12 deficiency. Finally, there is both experimental and clinical evidence to suggest that folate deficiency may interfere with immunologic status and may be associated with an increased predisposition to neoplasia. Nutritional as well as genetic factors may contribute to these various nonhematological manifestations of folate insufficiency.
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PMID:Folate deficiency beyond megaloblastic anemia: hyperhomocysteinemia and other manifestations of dysfunctional folate status. 993 May 68

An instructive case of isolated congenital folate malabsorption provides insight into the understanding of this rare disease. Folate loading tests with both timed serum and cerebrospinal fluid folate determinations suggest that both of the two mechanisms involved in gastrointestinal folate absorption are defective in this condition.
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PMID:Isolated congenital malabsorption of folic acid in a male infant: insights into treatment and mechanism of defect. 1054 60

Folic acid (folate) levels were measured in the serum of patients with various neurological diseases in Japan. Thirty-six patients showed decreased serum folate levels among 343 consecutive neurological patients (10.5%). Folate administration (15 mg/d) to folate-deficient patients improved neurological symptoms in 24 of 36 cases (67%). Serum folate levels were significantly lower in female than in male folate-deficient patients. Folate-deficient patients showed predominantly axonal neuropathy, which responded to folate supplementation more markedly. Male patients more frequently exhibited neuropathy, especially demyelinating and motor-dominant neuropathy, than females. Anemia was correlated with male sex and low serum folate levels. Male patients were more responsive than females to folate treatment. More male patients had taken excess alcohol or received gastrectomies than females. Neurological symptoms were more frequently improved by folate supplementation in patients with neuropathy than exclusive encephalopathy. Serum folate levels were lower in patients with encephalopathy, especially those with dementia, while folate therapy was more effective in neurological patients without dementia. Dysgeusia and anemia improved in all patients after folate administration. Neurological patients with malabsorption or treated with continuous drip infusion were resistant to folate therapy. Since folate-responsive neuroencepahlopathies are not rare among patients with neurological diseases in Japan, the serum folate level would serve as a valuable indicator for folate supplement therapy.
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PMID:Folic acid-responsive neurological diseases in Japan. 1157 72

The data generated from the human genome project offers unprecedented opportunities to elucidate the etiology of chronic diseases and developmental anomalies that arise from deleterious genome-diet interactions. Folate metabolism is an attractive system to explore such relationships. Folate is necessary for the synthesis of purine and thymidine deoxyribonucleotides and S-adenosylmethionine, a cofactor required for DNA methylation. Impaired folate metabolism results from primary folate deficiency, alcohol, gastrointestinal disorders that result in malabsorption, single nucleotide polymorphisms, increased folate catabolism and secondary nutrient deficiencies in vitamin B-6, vitamin B-12 and iron arising from a variety of pathologies. Any of these conditions singly or in combination influence DNA synthesis, DNA integrity, allelic-specific gene expression, chromatin structure and DNA mutation rates. Biochemical manifestations of impaired folate metabolism include increased uracil uptake into DNA, altered DNA methylation status and elevated homocysteine and S-adenosylhomocysteine in serum and tissues. These biochemical changes are associated with risk for cancer, cardiovascular disease, neural tube defects and some neuropathies and anemia, although direct causative mechanisms have not been established in all cases. Interactions between folate and the genome are reciprocal; polymorphisms in key genes influence folate nutritional requirements, indicating that dietary folate adequacy likely exerts selective pressure and thereby influences genetic variation. Other studies indicate that exposure to excess folate, perhaps at levels that occur at the upper end of the intake distribution curve, may have unintended consequences in promoting embryo viability. Therefore individualizing folic acid dietary recommendations necessitates a detailed understanding of all genetic and physiological variables that influence the interaction of folate with the genome and their relationship to the disease process.
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PMID:Bringing individuality to public health recommendations. 1216 15


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