vitamin-b-12 and Hemochromatosis

Dysregulation of iron homeostasis is implicated in Alzheimer's disease (AD). In this pilot study, common variants of the apolipoprotein E (APOE) and HFE genes resulting in the iron overload disorder of hereditary hemochromatosis (C282Y, H63D and S65C) were evaluated as factors in sporadic AD in an Ontario sample in which folic acid fortification has been mandatory since 1998. Laboratory studies also were done to search for genetic effects on blood markers of iron status, red cell folates and serum B12. Participants included 58 healthy volunteers (25 males, 33 females) and 54 patients with probable AD (20 males, 34 females). Statistical analyses were interpreted at the 95% confidence level. Contingency table and odds ratio analyses supported the hypothesis that in females of the given age range, E4 significantly predisposed to AD in the presence but not absence of H63D. In males, E4 significantly predisposed to AD in the absence of H63D, and H63D in the absence of E4 appeared protective against AD. Among E4+ AD patients, H63D was associated with significant lowering of red cell folate concentration, possibly as the result of excessive oxidative stress. However, folate levels in the lowest population quartile did not affect the risk of AD. A model is presented to explain the experimental findings.

Topics: Aged, 80 and over; Alleles; Alzheimer Disease; Apolipoprotein E4; Biomarkers; DNA Mutational Analysis; Erythrocytes; Female; Folic Acid; Genetic Predisposition to Disease; Genetic Variation; Genotype; Hemochromatosis; Hemochromatosis Protein; Histocompatibility Antigens Class I; Humans; Iron Overload; Male; Membrane Proteins; Mental Status Schedule; Middle Aged; Ontario; Sex Factors; Vitamin B 12

We report the case of a 54-year-old patient presenting with a typical pernicious anaemia. His mother was diagnosed with unquestionable pernicious anaemia 5 years previously. Serum ferritin was strongly increased (1,160 microg/l, normal range 29-380), with a transferrin saturation of 95%. We found a homozygous C282Y mutation of the HFE gene in our patient, his mother being heterozygous. The son of our patient was compound C282Y/H63D heterozygous without detectable pernicious anaemia. This seems to be the first report of an association between familial pernicious anaemia and hereditary haemochromatosis. The simultaneous occurrence of the 2 diseases in the same patient helps to delineate the relative contribution of each of them to iron metabolism and erythropoiesis: iron overload was only moderately increased and responded rapidly to phlebotomies, whereas haemochromatosis did not modify the cytologic presentation of pernicious anaemia.

Topics: Adult; Anemia, Pernicious; Hemochromatosis; Hemochromatosis Protein; Histocompatibility Antigens Class I; Humans; Male; Membrane Proteins; Middle Aged; Mutation; Vitamin B 12

Hereditary hemochromatosis is inherited as an autosomal recessive trait. It is characterized by increased absorption of dietary iron. The association between pernicious anaemia and hereditary hemochromatosis has never been described.. We report a case of paradoxical association of hereditary hemochromatosis and pernicious anaemia.. It seems that pernicious anaemia may prevent manifestations of hemochromatosis. We suppose that this protective role is due to atrophic body gastritis with iron malabsorption.

Topics: Aged; Anemia, Pernicious; Bloodletting; Ferritins; Follow-Up Studies; Hemochromatosis; Humans; Male; Mutation; Time Factors; Transferrin; Treatment Outcome; Vitamin B 12

Limited red blood cell (RBC) regeneration often prevents collection of sufficient blood from autologous donors. We studied the effects of subcutaneous recombinant erythropoietin (rEPO) in subjects making frequent blood donations. Six healthy iron-replete male subjects took rEPO (200 U/kg) subcutaneously daily, and donated blood (450 mL) twice a week for 3 weeks. During a control study, these subjects also attempted twice-weekly blood donations without rEPO. Four other males given rEPO, including one with idiopathic hemochromatosis, waited until day 8 to begin blood donations. All healthy subjects took oral ferrous sulfate. Subcutaneous rEPO given with blood donations resulted in a marked reticulocytosis (mean peak value 568 +/- 159 x 10(9)/L v 235 +/- 77 x 10(9)/L, control study; P < .05), and enhanced RBC production at 28 days (1,208 +/- 227 mL v 719 +/- 161 mL, P < .05). rEPO in advance of blood donations was slightly less effective in normal subjects (941 +/- 139 mL, P < .05); however, the subject with hemochromatosis produced substantially more RBCs (1,764 mL) than any normal subject. rEPO-treated normal subjects (but not the rEPO-treated patient with hemochromatosis or untreated controls) produced iron-deficient RBCs with elevated zinc protoporphyrin levels and low hemoglobin content. These cells appeared within 1 week of rEPO administration and before laboratory confirmation of depleted iron stores. Thus, subcutaneous rEPO is an effective stimulant of erythropoiesis in nonanemic blood donors. However, in addition to eventual depletion of iron stores, early functional iron deficiency affects response to the drug.

Topics: Blood Donors; Erythrocyte Count; Erythrocyte Indices; Erythropoiesis; Erythropoietin; Ferritins; Ferrous Compounds; Folic Acid; Hematocrit; Hemochromatosis; Hemoglobins; Humans; Iron; Iron Deficiencies; Male; Recombinant Proteins; Reticulocytes; Transferrin; Vitamin B 12

A rare case of long-term bone marrow failure with skin pigmentation is presented. The patient was a female with a long history of anemia and skin pigmentation since childhood, although she had no malformations nor chromosomal abnormalities. Hematological improvement has been maintained by the administration of prednisolone. This case may differ from other disorders known as congenital aplastic anemia.

Topics: Addison Disease; Anemia, Megaloblastic; Anemia, Refractory; Child; Chromosome Aberrations; Fanconi Anemia; Female; Graves Disease; Hemochromatosis; Humans; Pancytopenia; Pigmentation Disorders; Skin Pigmentation; Steroids; Vitamin B 12

Topics: Adolescent; Adult; Ascites; Bed Rest; Bloodletting; Child; Child, Preschool; Cholestyramine Resin; Dietary Fats; Dietary Proteins; Diuretics; Energy Intake; Female; Hemochromatosis; Hepatic Encephalopathy; Hepatolenticular Degeneration; Humans; Lactulose; Liver Cirrhosis; Liver Cirrhosis, Biliary; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Penicillamine; Potassium; Vitamin B 12

Topics: Anemia, Hypochromic; Dosage Forms; Drug Combinations; Drug Compounding; Folic Acid; Folic Acid Deficiency; Hematopoiesis; Hemochromatosis; Humans; Infusions, Parenteral; Iron; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Hemolytic; Anemia, Pernicious; Erythropoiesis; Hemochromatosis; Humans; Iron; Spherocytosis, Hereditary; Splenectomy; Tablets; Thalassemia; Vitamin B 12

Topics: Adolescent; Adult; Aged; Anemia; Choline; Female; Folic Acid; Hemochromatosis; Humans; Hydroxybutyrates; Liver Diseases; Male; Middle Aged; Niacinamide; Phosphoric Acids; Pyridoxine; Vitamin B 12

Topics: Alcoholism; Anemia; Anemia, Hypochromic; Blood Chemical Analysis; Blood Volume; Bone Marrow Examination; Erythropoiesis; Folic Acid; Folic Acid Deficiency; Gastric Juice; Hematocrit; Hemochromatosis; Hemolysis; Humans; Iron; Liver; Liver Cirrhosis; Liver Diseases; Melena; Metabolism; Splenomegaly; Vitamin B 12

Topics: Anemia; Anemia, Macrocytic; Anemia, Megaloblastic; Drug Therapy; Folic Acid; Hemochromatosis; Humans; Vitamin B 12

Topics: Anemia; Anemia, Macrocytic; Anemia, Megaloblastic; Blood Chemical Analysis; Diet; Diet Therapy; Drug Therapy; FIGLU Test; Folic Acid; Folic Acid Deficiency; Geriatrics; Hematinics; Hemochromatosis; Humans; Liver Cirrhosis; Liver Function Tests; Metabolism; Vitamin B 12

Topics: Blood Chemical Analysis; Choline; Diet; Folic Acid; Folic Acid Deficiency; Hematocrit; Hemochromatosis; Iron; Lipotropic Agents; Liver; Neomycin; Pancreas; Pantothenic Acid; Pharmacology; Pyridoxine; Rats; Research; Sucrose; Vitamin B 12; Vitamin B Complex

Topics: Anemia; Anemia, Hemolytic; Anemia, Hypochromic; Anemia, Pernicious; Blood Coagulation; Blood Proteins; Chloramphenicol; Epidemiology; Epoetin Alfa; Erythropoietin; Haptoglobins; Hematologic Diseases; Hematology; Hemochromatosis; Humans; Iron-Dextran Complex; Leukemia; Polycythemia; Thromboplastin; Vitamin B 12

Topics: Anemia; Anemia, Macrocytic; Anemia, Megaloblastic; Bone Marrow Examination; Fatty Liver; Folic Acid; Gastrectomy; Hemochromatosis; Hemosiderosis; Humans; Iron; Liver Cirrhosis; Vitamin B 12; Vitamin B Deficiency

Topics: Anemia; Corrinoids; Hematinics; Hemochromatosis; Hepatolenticular Degeneration; Humans; Iron; Pharmacology; Thiamine; Thioctic Acid; Vitamin B 12