intrinsic-factor and Folic-Acid-Deficiency

At one time, the diagnosis of a deficiency of vitamin B12 or folate was considered to be relatively straightforward. As knowledge has accumulated, the limitations of such tests as serum vitamin level measurements and the Schilling test have become apparent. With the development of newer tests, atypical and subclinical deficiency states have been recognized. In this review, available tests used in the diagnosis of vitamin B12 and folate deficiency are discussed, and a rational approach to the diagnosis of these deficiency states is presented.

Topics: Antibodies; Clinical Laboratory Techniques; Clinical Trials as Topic; Decision Trees; Diagnosis, Differential; Erythrocytes; Folic Acid Deficiency; Hematologic Diseases; Homocysteine; Humans; Intrinsic Factor; Methylmalonic Acid; Nervous System Diseases; Parietal Cells, Gastric; Primary Health Care; Schilling Test; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Pernicious; Diagnosis, Differential; Folic Acid; Folic Acid Deficiency; Humans; Hydrolysis; Intestinal Absorption; Intestinal Mucosa; Intrinsic Factor; Malabsorption Syndromes; Pancreas; Pteroylpolyglutamic Acids; Sprue, Tropical; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adolescent; Adult; Anemia, Hemolytic; Anemia, Macrocytic; Anemia, Megaloblastic; Anemia, Pernicious; Biological Transport; Bone Marrow; Bone Marrow Cells; Child; Child, Preschool; Female; Folic Acid; Folic Acid Deficiency; Homocystinuria; Humans; Infant; Intrinsic Factor; Malabsorption Syndromes; Male; Metabolism, Inborn Errors; Methionine; Methionine Adenosyltransferase; Orotic Acid; Phenylketonurias; Tetrahydrofolate Dehydrogenase; Transcobalamins; Vitamin B 12

1. Low serum B12 levels can be measured with considerable precision by microbiological assay with the Euglena gracilis assay and B12 deficiency can be recognised with a high level of consistency by either the Euglena or L. leichmannii assays. Either method is ideally suited for the assay of large numbers of specimens. The Lactobacillus leichmanii technique requires preliminary extraction of protein and it has been suggested that this may be a source of inaccuracy. 2. The radioisotope dilution assay should be the ideal method of measuring B12 levels in small or moderate numbers of specimens for it is a simple method that can be carried out in any laboratory with suitable counting equipment. After many false starts the conditions required for accurate assay are now understood. Each of 40 to 50 radioisotopic dilution techniques that have been introduced claims to be capable of differentiating B12 deficiency from control subjects but the reported correlations between the actual levels found in the two different assays are variable and the levels may be much higher with some radioisotopic methods. 3. The subnormal serum levels which are found in pernicious anaemia with all these techniques indicate severe reduction of the liver B12 level. A low serum B12 level in other conditions has, in the absence of associated folate or iron deficiency, the same significance. If the fall in the serum B12 level is associated with folate or iron deficiency, the tissue B12 levels are usually reduced but not to the low levels found in B12 deficiency states. 4. In practice, a subnormal B12 level is a valuable pointer not only to unsuspected pernicious anaemia but also to other gastrointestinal or nutritional disorders. The significance of a fall in the B12 level can only be understood if its cause is defined by a full clinical and gastroenterological investigation. 5. Falsely low serum B12 levels are found under certain iatrogenic conditions and B12 levels may be normal in spite of cellular deficiency of B12 under the rare circumstances of pernicious anaemia being associated with chronic myeloid leukaemia or when there is deficiency of TC 2.

Topics: Anemia, Megaloblastic; Anemia, Pernicious; Ascorbic Acid; Biological Assay; Bone Marrow; Bone Marrow Cells; Carrier Proteins; Deoxyuridine; Euglena gracilis; Female; Folic Acid Deficiency; Humans; Intrinsic Factor; Lactobacillus; Leukemia, Myeloid; Male; Pregnancy; Pregnancy Complications; Radioisotope Dilution Technique; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Alcoholism; Anemia, Hypochromic; Anemia, Macrocytic; Anemia, Pernicious; Diagnosis, Differential; Folic Acid; Folic Acid Antagonists; Folic Acid Deficiency; Humans; Intestinal Absorption; Intrinsic Factor; Malabsorption Syndromes; Pyrimidine Nucleotides; Thymine Nucleotides; Uracil Nucleotides; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Age Factors; Diet; Female; Folic Acid; Folic Acid Deficiency; Gastrointestinal Diseases; Humans; Infant; Intrinsic Factor; Malabsorption Syndromes; Metabolic Diseases; Metabolism, Inborn Errors; Nutrition Disorders; Nutritional Physiological Phenomena; Nutritional Requirements; Pregnancy; Time Factors; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Achlorhydria; Anemia, Pernicious; Animals; Binding Sites; Biological Transport; Blind Loop Syndrome; Cestode Infections; Folic Acid Deficiency; Humans; Intestinal Absorption; Intestine, Small; Intrinsic Factor; Liver; Malabsorption Syndromes; Pancreas; Postgastrectomy Syndromes; Protein Binding; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Macrocytic; Bile; Binding Sites; Feces; Folic Acid; Folic Acid Deficiency; Humans; Intestinal Absorption; Intrinsic Factor; Protein Binding; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Macrocytic; Anemia, Pernicious; Child; Child, Preschool; Diphyllobothriasis; Female; Folic Acid Deficiency; Humans; Infant; Infant Nutrition Disorders; Infant, Newborn; Intrinsic Factor; Kwashiorkor; Malabsorption Syndromes; Male; Proteinuria; Thiamine; Transferases; Vitamin B 12 Deficiency

Topics: Anemia; Anemia, Hypochromic; Anemia, Macrocytic; Female; Folic Acid Deficiency; Gastrectomy; Humans; Intestinal Absorption; Intrinsic Factor; Iron; Vitamin B 12 Deficiency

Topics: Anemia, Megaloblastic; Anemia, Pernicious; Autoantibodies; Autoimmune Diseases; Folic Acid Deficiency; Gastritis, Atrophic; Humans; Intrinsic Factor; Parietal Cells, Gastric; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Administration, Oral; Anemia, Megaloblastic; Anemia, Pernicious; Antibodies; Folic Acid; Folic Acid Deficiency; Humans; Injections, Intramuscular; Intrinsic Factor; Leucovorin; Schilling Test; Vitamin B 12; Vitamin B Complex

We present a case of extreme pancytopenia in a 27-year-old pregnant woman. The initial picture was compatible with a severe hematological problem in the category of aplastic anemia, paroxysmal nocturnal hemoglobinuria or even acute leukemia. The further biochemical investigations revealed, however, a folate deficiency. Nowadays this is a very rare cause of pancytopenia. Next to this she also had a Vitamin B(12) deficiency due to intrinsic factor failure. The recent literature is discussed.

Topics: Adult; Anemia, Megaloblastic; Blood Transfusion; Bone Marrow; Female; Folic Acid; Folic Acid Deficiency; Humans; Infant, Newborn; Intrinsic Factor; Male; Pancytopenia; Platelet Transfusion; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Vitamin B 12; Vitamin B 12 Deficiency

To determine whether the increased prevalence of low serum cobalamin concentrations in elderly people represents true deficiency, serum concentrations of cobalamin and folate and of metabolites that are sensitive indicators of cobalamin deficiency were measured in 548 surviving members of the original Framingham Study cohort. Serum cobalamin concentrations < 258 pmol/L were found in 222 subjects (40.5%) compared with 17.9% of younger control subjects (P < 0.001). Serum methylmalonic acid and total homocysteine concentrations were markedly elevated in association with cobalamin values < 258 pmol/L in 11.3% and 5.7%, respectively, of the cohort. Both metabolites were increased in 3.8% of the cohort, associated with significantly lower erythrocyte counts and higher mean cell volumes. Serum metabolites correlated best with serum cobalamin values, even when subnormal determinations were excluded. The prevalence of cobalamin deficiency was > or = 12% in a large sample of free-living elderly Americans. Many elderly people with "normal" serum vitamin concentrations are metabolically deficient in cobalamin or folate.

Topics: Adult; Aged; Aged, 80 and over; Aging; Cohort Studies; Female; Folic Acid Deficiency; Gas Chromatography-Mass Spectrometry; Homocysteine; Humans; Intrinsic Factor; Male; Massachusetts; Methylmalonic Acid; Middle Aged; Prevalence; Radioimmunoassay; Reference Values; Surveys and Questionnaires; Vitamin B 12 Deficiency

Topics: Adolescent; Anemia, Megaloblastic; Child; Child, Preschool; Female; Folic Acid Deficiency; Humans; Infant; Intestinal Absorption; Intrinsic Factor; Male; Transcobalamins; Vitamin B 12 Deficiency

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Anemia, Pernicious; Bone Marrow Cells; DNA; Ferritins; Folic Acid Deficiency; Intestinal Mucosa; Intrinsic Factor; Iron; Myelin Sheath; Schilling Test; Vitamin B 12 Deficiency

Topics: Alcoholism; Celiac Disease; Exocrine Pancreatic Insufficiency; Folic Acid; Folic Acid Deficiency; Gastric Mucosa; Glutamates; Humans; Ileum; Intestinal Absorption; Intrinsic Factor; Malabsorption Syndromes; Protein Binding; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

Because virtually all cases of vitamin B12 deficiency seen in this country are due to malabsorption, the availability of radioactive vitamin B12 for direct measurement of absorption of this essential nutrient has proved to be of great clinical value. These tests are useful not only in demonstrating vitamin B12 malabsorption but also often in defining the pathophysiological mechanism responsible for this abnormality. The urinary excretion test of Schilling remains the most useful test for vitamin B12 absorption. Minor precautions and modifications in technique make the test results more reliable and easier to interpret. The 8-hr plasma test for vitamin B12 absorption can no longer be considered acceptable. Some patients with vitamin B12 malabsorption have results in the normal range when studied by this method. Serum vitamin B12 assays utilizing radioactive vitamin B12 and the isotope dilution principle are not widely used and are useful screening tests. Low normal or borderline results observed in patients with clinical evidence suggestive of vitamin B12 deficiency should be interpreted with caution or confirmed by radioactive vitamin B12 absorption studies. Radioactive vitamin B12 can also be used for rapid, reliable assay of gastric intrinsic factor, antibody to intrinsic factor and unsaturated vitamin B12 serum. Methods using radioactive folate compounds for similar in vivo and in vitro studies are not yet applicable for routine use in nuclear medicine laboratories.

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Anemia, Pernicious; Cobalt Radioisotopes; Erythrocytes; Folic Acid; Folic Acid Deficiency; Humans; Intestinal Absorption; Intrinsic Factor; Radioimmunoassay; Radioisotope Dilution Technique; Schilling Test; Tritium; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Pernicious; Animals; Biological Assay; Blood Proteins; Chickens; Cobalt Radioisotopes; Euglena gracilis; Female; Folic Acid Deficiency; Humans; Intrinsic Factor; Lactobacillus; Leukemia, Myeloid; Polycythemia Vera; Postgastrectomy Syndromes; Pregnancy; Protein Binding; Radioisotope Dilution Technique; Umbilical Cord; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Afferent Loop Syndrome; Anemia, Macrocytic; Diarrhea; Dumping Syndrome; Folic Acid Deficiency; Gastrectomy; Gastric Juice; Gastrins; Humans; Intestinal Absorption; Intrinsic Factor; Mucus; Osteoporosis; Postgastrectomy Syndromes; Stomach Neoplasms; Vitamin B 12 Deficiency; Vomiting

The blood concentrations of vitamin B12 and folate, which are very useful in diagnosis of megaloblastic anemia and of these factors' dificiencies, are actually measured by precise, rapid, and specific competitive binding radioassays. Futher clinical advantages can be reached with the application of other in vitro radioisotope techniques, such as radioassay of IF, of antibodies anti-IF, of transcobalamins, and of FABP (folic acid binding protein). The major impact of the vitamin B12, folates and other related radioassays has been to permit more Hospitals and laboratories to do these determinations, replacing the more time-consuming, relatively imprecise, and often artifactual microbiological assays.

Topics: Anemia, Megaloblastic; Anemia, Sideroblastic; Antibodies; FIGLU Test; Folic Acid; Folic Acid Deficiency; Intrinsic Factor; Radioimmunoassay; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Pernicious; Female; Folic Acid Deficiency; Humans; Intrinsic Factor; Male; Middle Aged; Schilling Test; Vitamin B 12 Deficiency

Topics: Anemia; Anemia, Hypochromic; Anemia, Pernicious; Anemia, Sideroblastic; Blind Loop Syndrome; Crohn Disease; Diverticulitis; Folic Acid Deficiency; Gastritis; Gastrointestinal Diseases; Gastrointestinal Hemorrhage; Gastrointestinal Neoplasms; Humans; Intrinsic Factor; Malabsorption Syndromes; Vitamin B 12 Deficiency; Whipple Disease

Topics: Anemia, Pernicious; Charcoal; Cobalt Isotopes; Cyanides; Euglena gracilis; Folic Acid Deficiency; Gastric Juice; Hemoglobins; Humans; Intrinsic Factor; Radioisotope Dilution Technique; Vitamin B 12

Topics: Achlorhydria; Anemia, Macrocytic; Anemia, Pernicious; Autoantibodies; Cobalt Isotopes; Folic Acid Deficiency; Gastric Juice; Humans; Intrinsic Factor; Radioimmunoassay; Vitamin B 12

Topics: Adolescent; Anemia, Macrocytic; Anemia, Pernicious; Diet; Female; Folic Acid Deficiency; Humans; Intrinsic Factor; Male; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Macrocytic; Anemia, Pernicious; Anticonvulsants; Ascorbic Acid Deficiency; Contraceptives, Oral; Diagnosis, Differential; Folic Acid; Folic Acid Deficiency; Gastric Juice; Humans; Intrinsic Factor; Nutritional Requirements; Schilling Test; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Macrocytic; Folic Acid Deficiency; Humans; Intellectual Disability; Intestinal Absorption; Intrinsic Factor; Metabolism, Inborn Errors; Orotic Acid; Transferases; Vitamin B 12 Deficiency

Three patients are described, and they provide further evidence that deficiency of folic acid and vitamin B(12) may sometimes affect small intestinal function. Malabsorption of both xylose and vitamin B(12) returned to normal in one patient after treatment of a megaloblastic anaemia due to dietary deficiency of folic acid. Impaired absorption of vitamin B(12) was corrected by vitamin B(12) therapy in the other two patients. The initial cause of the vitamin B(12) deficiency in one patient was not apparent, but she was taking Gynovlar 21, which may have been an aetiological factor. In the third patient the small intestinal defect was secondary to pernicious anaemia, and in a group of 98 other patients with pernicious anaemia intrinsic factor did not improve vitamin B(12) absorption in six, and only partially corrected absorption in 30. The significance of these observations is discussed.

Topics: Adult; Anemia, Macrocytic; Anemia, Pernicious; Contraceptives, Oral; Female; Folic Acid; Folic Acid Deficiency; Humans; Intestinal Absorption; Intestine, Small; Intrinsic Factor; Malabsorption Syndromes; Vitamin B 12; Vitamin B 12 Deficiency; Xylose

Topics: Affective Symptoms; Aged; Anemia, Pernicious; Antibodies; Cognition Disorders; Dementia; Female; Folic Acid Deficiency; Gastric Mucosa; Humans; Intracranial Arteriosclerosis; Intrinsic Factor; Male; Mental Disorders; Schilling Test; Vitamin B 12 Deficiency

Topics: Adult; Aged; Aged, 80 and over; Anemia, Megaloblastic; Anemia, Pernicious; Antibodies; Arthritis, Rheumatoid; Female; Folic Acid Deficiency; Humans; Intrinsic Factor; Male; Middle Aged; Vitamin B 12 Deficiency

Topics: Achlorhydria; Adult; Aged; Anemia, Macrocytic; Anemia, Pernicious; Black People; Cobalt Isotopes; Female; Folic Acid Deficiency; Humans; Intrinsic Factor; Male; Middle Aged; Radiometry; Vitamin B 12; Vitamin B 12 Deficiency; White People

Topics: Adult; Female; Folic Acid; Folic Acid Deficiency; Humans; Intestinal Absorption; Intrinsic Factor; Male; Pregnancy; Pregnancy Complications, Hematologic; Schilling Test; Vitamin B 12

Topics: Anemia; Anemia, Hypochromic; Anemia, Macrocytic; Carbachol; Celiac Disease; Cobalt Isotopes; Colonic Neoplasms; Duodenal Ulcer; Folic Acid; Folic Acid Deficiency; Gastric Acidity Determination; Gastric Juice; Histamine; Humans; Insulin; Intrinsic Factor; Male; Pharmacology; Physiology; Sprue, Tropical; Vitamin B 12

Topics: Anemia; Anemia, Macrocytic; Anemia, Pernicious; Black People; Blood Chemical Analysis; Bone Marrow; Deficiency Diseases; Drug Therapy; Folic Acid; Folic Acid Deficiency; Gastric Juice; Gastric Mucosa; Glutamates; Hematopoiesis; Humans; Hydrochloric Acid; Intrinsic Factor; Pathology; Pharmacology; Urine; Vitamin B 12

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Blood Cell Count; Deficiency Diseases; Drug Therapy; Female; Folic Acid; Folic Acid Deficiency; Humans; Intrinsic Factor; Malabsorption Syndromes; Metabolism; Pregnancy; Pregnancy Complications; Pregnancy Complications, Hematologic; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia; Anemia, Macrocytic; Animals; Folic Acid; Folic Acid Deficiency; Gastric Juice; Humans; Intrinsic Factor; Rats; Vitamin B 12; Vitamin B Complex