Anemia, megaloblastic

Deficiency. Macrocytic anemia, megaloblastic anemia, and neurological symptoms characterize vitamin B 2 deficiency. Alterations in hematopoiesis occur because of the high requirement for vitamin B 2 for normal DNA repHcation necessary to sustain the rapid turnover of the erythrocytes. Abnormal DNA repHcation secondary to vitamin B 2 deficiency produces a defect in the nuclear maturational process of committed hematopoietic stem cells. As a result, the erythrocytes are either morphologically abnormal or die during development. 

B,2 Cobalamin Coenzyme in transfer of one-carbon fragments and metabolism of folic acid Pernicious anemia = megaloblastic anemia with degeneration of the spinal cord... 

Macrocytic anemias Megaloblastic anemias Vitamin B12 deficiency Folic acid deficiency anemia Microcytic hypochromic anemias Iron-deficiency anemia Genetic anomaly Sickle cell anemia Thalassemia... 

Megaloblastic anemia Megaloblastic anemia Progressive peripheral neuropathy... 

There are several acquired hematological disorders which have an increased synthesis of Hb-F [summarized in (H37, K13)], Thus, an elevated level of Hb-F is frequently observed in, for example, Fanconi s anemia, megaloblastic anemia, polycythemia vera, various types of leukemia, multiple myeloma and lymphomas, macroglobulinemia, and metastatic disease of the bone marrow. The chemical heterogeneity of the Hb-F in some of these disorders (aplastic anemia, Fanconi s anemia, and various forms of leukemia) has been studied (H60, R29). In many instances, the to ratio is similar to that found in the normal newborn. This is particularly striking for patients with various forms of leukemia, and the Hb-F which is produced in increased quantities in these disorders invariably has a °y to y ratio of about 3 1. This newborn ratio of °y to y chains in Hb-F may be a common factor in these diseases as perhaps another example of fetal characteristics in red cells of patients with leukemia, it supports the hypothesis that these cells may be of fetal origin (H25). 

Sideroblastic anemia is characterized by the accumulation of iron in the mitochondria of erythroblasts. In a Phase I study in 35 patients with refractory tumors, eight taking CMT-3 developed anemia without leukopenia or thrombocytopenia (54). Three of these patients underwent bone-marrow examination and each had ringed side-roblasts. The authors referred to several cases of aplastic anemia, megaloblastic anemia, and hemolytic anemia in which members of the tetracycline family have been implicated. However, they stated that there has been no previous reports of sideroblastic anemia associated with any tetracycline derivative and that the molecular mechanisms by which CMT-3 might cause sideroblastic anemia are unclear. 

PA is characterized by megaloblastic anemia, megaloblastic marrow, and, occasionally, neurological symptoms. The hematological characteristics of the disease are indistinguishable from those of folate d idency. The biochemical signs of the disease include low serum B12 and elevated MMA. The neurological problems affect about 25% of those with the disease and include numbness of the feet and... 

There is also a significantly increased incidence of IgA deficiency in patients with autoimmune or potentially autoimmune disorders, and usually it is not clear which came first. It can be argued that autoimmunity is a complication of immune imbalance subsequent to inborn IgA deficiency (H24). With inborn absence of IgA, exposure to normal human colostrum, plasma, and saliva can result in the production of antibodies to IgA. By the time such patients are discovered the etiological mechanisms are often obscured and IgA treatment is out of the question. The incidence of IgA deficiency is known to be 1-4% in the following conditions Still s disease, systemic lupus erythematosus, rheumatoid arthritis, Sjogren s disease, warm hemolytic anemia, megaloblastic anemia, idiopathic pulmonary hemosiderosis, thyrotoxicosis, and cirrhosis. 

Folate deficiency results in megaloblastic anemia. Megaloblastic anemia is characterized by macrocytic erythrocytes produced by abnormal proliferation of erythroid precursors in the bone marrow. Folate deficiency encumbers the maturation of these cells by inhibition of DNA synthesis. Without an adequate supply of folate, DNA synthesis is limited by decreased purine and dTMP levels. 

Pernicious anemia megaloblastic anemia due to lack of intrin-sic factor and B12 malabsorption... 

A. Iron and Vitamin Deficiency Anemias Microcytic hypochromic anemia, caused by iron deficiency, is the most common type of anemia. Megaloblastic anemias are caused by a deficiency of vitamin B, or folic acid, cofactors required for the normal maturation of red blood cells. Pernicious anemia, the most common type of vitamin Bj, deficiency anemia, is caused by a defect in the synthesis of intrinsic factor, a protein required for efficient absorption of dietary vitamin B 2, or by surgical removal of that part of the stomach that secretes intrinsic factor. 

Also see ANEMIA, section headed "Groups of Persons Susceptible to Nutritional Anemias" ANEMIA, MEGALOBLASTIC FOLIC ACID INFANT ANEMIA IRON and PREGNANCY AND LACTATION NUTRITION.)... 

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