Disease relevance of Anemia, Megaloblastic

• Homocystinuria and megaloblastic anemia responsive to vitamin B12 therapy. An inborn error of metabolism due to a defect in cobalamin metabolism [1].
• Thiamine-responsive megaloblastic anemia, also known as "TRMA" or "Rogers syndrome," is an early-onset autosomal recessive disorder defined by the occurrence of megaloblastic anemia, diabetes mellitus, and sensorineural deafness, responding in varying degrees to thiamine treatment [2].
• Patients of the cblE complementation group of disorders of folate/cobalamin metabolism who are defective in reductive activation of methionine synthase exhibit megaloblastic anemia, developmental delay, hyperhomocysteinemia, and hypomethioninemia [3].
• However, no metabolic evidence for vitamin B12 deficiency was demonstrable, although the patient initially had megaloblastic anemia apparently due to folate deficiency [4].
• Thus, the folate-deficient mice had "ineffective hematopoiesis" leading to pancytopenia, and they therefore provide a murine model of megaloblastic anemia [5].

Psychiatry related information on Anemia, Megaloblastic

• These observations demonstrate that chronic alcohol consumption impairs folate coenzymes, accelerates appearance of hematologic indices of megaloblastic anemia, and causes possible malabsorption of enterohepatically circulated folates in folate deficiency even when other essential nutrients are provided [6].
• Features of a severe phenotype, first identified in patients of Japanese descent, include elevated levels of formiminoglutamate (FIGLU) in the urine in response to histidine administration, megaloblastic anemia, and mental retardation [7].
• Her megaloblastic anemia was caused by vitamin B12 and folate deficiencies, resulting from an inadequate diet and alcohol abuse [8].

High impact information on Anemia, Megaloblastic

• Amnionless, essential for mouse gastrulation, is mutated in recessive hereditary megaloblastic anemia [9].
• Uracil in DNA in megaloblastic anemia [10].
• Studies of a patient with megaloblastic anemia and an abnormal transcobalamin II [11].
• Dihydrofolate reductase deficiency causing megaloblastic anemia in two families [12].
• The deoxyuridine suppression test identifies subtle cobalamin deficiency in patients without typical megaloblastic anemia [13].

Chemical compound and disease context of Anemia, Megaloblastic

• Three siblings presented in their second year of life with megaloblastic anemia that responded to parenteral cobalamin (Cbl) [14].
• The megaloblastic anemia of cobalamin deficiency appears secondary to decreased methionine synthetase activity [15].
• Acute megaloblastic anemia induced by high-dose trimethoprim-sulfamethoxazole [16].
• Severe megaloblastic anemia complicating pyrimethamine therapy [17].
• These results indicate that decreased de novo synthesis of purines plays as important a role as decreased de novo synthesis of thymidylate in the pathogenesis of megaloblastic anemia [18].

Biological context of Anemia, Megaloblastic

• Apoptosis in megaloblastic anemia occurs during DNA synthesis by a p53-independent, nucleoside-reversible mechanism [18].
• We describe the range of MPXI levels in healthy and patient populations and in 10 cases of megaloblastic anemia, including five having elevated mean cell volume (MCV) and five without macrocytosis [19].
• Fibroblasts from patients with thiamine-responsive megaloblastic anemia (TRMA) syndrome with diabetes and deafness undergo apoptotic cell death in the absence of supplemental thiamine in their cultures [20].
• Depressed cell-mediated immunity in megaloblastic anemia due to folic acid deficiency [21].
• A mouse model of thiamin-responsive megaloblastic anemia (diabetes mellitus, deafness, megaloblastic anemia) lacking functional Slc19a2 has been generated and unexpectedly found to have a male-specific sterility phenotype [22].

Anatomical context of Anemia, Megaloblastic

• These findings indicate that the erythrocyte membrane protein pattern is abnormal in severe megaloblastic anemia and that this abnormality is not secondary to increased activity of the endogenous erythrocyte membrane proteinase [23].
• Neutrophil myeloperoxidase measurement uncovers masked megaloblastic anemia [19].
• Bone marrow cells from 15 patients with normal deoxyuridine (dU) suppression test results, 3 healthy subjects, and 11 patients with megaloblastic anemia caused by vitamin B12 or folate deficiency were examined for misincorporation of uracil into DNA [24].
• In humans, severe inhibition of methionine synthase results in the development of megaloblastic anemia, and eventually in subacute combined degeneration of the spinal cord [25].
• Vitamin B12 malabsorption in the ileum has been postulated as the underlying cause of the Imerslund-Grasbeck syndrome comprising megaloblastic anemia, proteinuria, and multiple neurological abnormalities [26].

Gene context of Anemia, Megaloblastic

• Loss of CUBN, the intestinal intrinsic factor (IF)-vitamin B12 receptor, results in hereditary megaloblastic anemia (MGA1), owing to vitamin B12 malabsorption [27].
• The spectrum of mutations, including four novel ones, in the thiamine-responsive megaloblastic anemia gene SLC19A2 of eight families [28].
• In genetic disorders that are characterized by congenital deficiency of TCII, intracellular Cbl deficiency occurs, resulting in an early onset of megaloblastic anemia that is sometimes accompanied by a neurologic disorder [29].
• E2F2 mutant mice show erythroid maturation defects that are comparable with those observed in patients with megaloblastic anemia [30].
• At that time, the amnionless (AMN) gene was not yet known to implicate in megaloblastic anemia [31].

Analytical, diagnostic and therapeutic context of Anemia, Megaloblastic

• Recent studies using anion exclusion chromatography have suggested that uracil is misincorporated into the DNA of patients with megaloblastic anemia to levels detectable by nonradioactive methods [32].
• Patients on regular hemodialysis treatment may develop megaloblastic anemia caused by folate deficiency, but whether folate supplementation is required is still controversial, particularly during erythropoietin administration [33].
• Iron inclusions in plasma cells of the bone marrow of an individual suffering from megaloblastic anemia due to folate deficiency were examined by electron microscopy [34].
• Megaloblastic anemia in an infant receiving total parenteral nutrition [35].

References