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| Congenital dyserythropoietic anemia type IV | |
|---|---|
| Specialty | Hematology  |
Congenital dyserythropoietic anemia type IV (CDA IV) has been described with typical morphologic features of CDA II but a negative acidified-serum test. [1]
CDA type IV is characterized by mild to moderate splenomegaly. Hemoglobin is very low and patients are transfusion dependent. MCV is normal or mildly elevated. Erythropoiesis is normoblastic or mildly to moderately megaloblastic. Nonspecific erythroblast dysplasia is present. [2]
Congenital dyserythropoietic anemia type IV is an autosomal dominant inherited red blood cell disorder characterized by ineffective erythropoiesis and hemolysis resulting in anemia. Circulating erythroblasts and erythroblasts in the bone marrow show various morphologic abnormalities. Affected individuals with CDAN4 also have increased levels of fetal hemoglobin. [3]
| Type | OMIM | Gene | Locus |
|---|---|---|---|
| CDAN4 | 613673 | KLF1 | 19p13.13-p13.12 |
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Treatment consists of frequent blood transfusions and chelation therapy. Potential cures include bone marrow transplantation and gene therapy.
Hemolysis or haemolysis, also known by several other names, is the rupturing (lysis) of red blood cells (erythrocytes) and the release of their contents (cytoplasm) into surrounding fluid. Hemolysis may occur in vivo or in vitro.
Anemia or anaemia is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. The name is derived from Ancient Greek: ἀναιμία anaimia, meaning 'lack of blood', from ἀν- an-, 'not' and αἷμα haima, 'blood'. When anemia comes on slowly, the symptoms are often vague, such as tiredness, weakness, shortness of breath, headaches, and a reduced ability to exercise. When anemia is acute, symptoms may include confusion, feeling like one is going to pass out, loss of consciousness, and increased thirst. Anemia must be significant before a person becomes noticeably pale. Symptoms of anemia depend on how quickly hemoglobin decreases. Additional symptoms may occur depending on the underlying cause. Preoperative anemia can increase the risk of needing a blood transfusion following surgery. Anemia can be temporary or long term and can range from mild to severe.
A myelodysplastic syndrome (MDS) is one of a group of cancers in which immature blood cells in the bone marrow do not mature, and as a result, do not develop into healthy blood cells. Early on, no symptoms typically are seen. Later, symptoms may include feeling tired, shortness of breath, bleeding disorders, anemia, or frequent infections. Some types may develop into acute myeloid leukemia.
Hemolytic anemia or haemolytic anaemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells (RBCs), either in the blood vessels or elsewhere in the human body (extravascular). This most commonly occurs within the spleen, but also can occur in the reticuloendothelial system or mechanically. Hemolytic anemia accounts for 5% of all existing anemias. It has numerous possible consequences, ranging from general symptoms to life-threatening systemic effects. The general classification of hemolytic anemia is either intrinsic or extrinsic. Treatment depends on the type and cause of the hemolytic anemia.
Erythropoiesis is the process which produces red blood cells (erythrocytes), which is the development from erythropoietic stem cell to mature red blood cell.
Megaloblastic anemia is a type of macrocytic anemia. An anemia is a red blood cell defect that can lead to an undersupply of oxygen. Megaloblastic anemia results from inhibition of DNA synthesis during red blood cell production. When DNA synthesis is impaired, the cell cycle cannot progress from the G2 growth stage to the mitosis (M) stage. This leads to continuing cell growth without division, which presents as macrocytosis. Megaloblastic anemia has a rather slow onset, especially when compared to that of other anemias. The defect in red cell DNA synthesis is most often due to hypovitaminosis, specifically vitamin B12 deficiency or folate deficiency. Loss of micronutrients may also be a cause.
Anemia of chronic disease (ACD) or anemia of chronic inflammation is a form of anemia seen in chronic infection, chronic immune activation, and malignancy. These conditions all produce elevation of interleukin-6, which stimulates hepcidin production and release from the liver. Hepcidin production and release shuts down ferroportin, a protein that controls export of iron from the gut and from iron storing cells. As a consequence, circulating iron levels are reduced. Other mechanisms may also play a role, such as reduced erythropoiesis. It is also known as anemia of inflammation, or anemia of inflammatory response.
Sideroblastic anemia, or sideroachrestic anemia, is a form of anemia in which the bone marrow produces ringed sideroblasts rather than healthy red blood cells (erythrocytes). In sideroblastic anemia, the body has iron available but cannot incorporate it into hemoglobin, which red blood cells need in order to transport oxygen efficiently. The disorder may be caused either by a genetic disorder or indirectly as part of myelodysplastic syndrome, which can develop into hematological malignancies.
GATA-binding factor 1 or GATA-1 is the founding member of the GATA family of transcription factors. This protein is widely expressed throughout vertebrate species. In humans and mice, it is encoded by the GATA1 and Gata1 genes, respectively. These genes are located on the X chromosome in both species.
Beta thalassemias are a group of inherited blood disorders. They are forms of thalassemia caused by reduced or absent synthesis of the beta chains of hemoglobin that result in variable outcomes ranging from severe anemia to clinically asymptomatic individuals. Global annual incidence is estimated at one in 100,000. Beta thalassemias occur due to malfunctions in the hemoglobin subunit beta or HBB. The severity of the disease depends on the nature of the mutation.
Basophilic stippling, also known as punctate basophilia, is the presence of numerous basophilic granules that are dispersed through the cytoplasm of erythrocytes in a peripheral blood smear. They can be demonstrated to be RNA. They are composed of aggregates of ribosomes; degenerating mitochondria and siderosomes may be included in the aggregates. In contrast to Pappenheimer bodies, they are negative with Perls' acid ferrocyanide stain for iron. Basophilic stippling is indicative of disturbed erythropoiesis. It can also be found in some normal individuals.
Congenital dyserythropoietic anemia (CDA) is a rare blood disorder, similar to the thalassemias. CDA is one of many types of anemia, characterized by ineffective erythropoiesis, and resulting from a decrease in the number of red blood cells (RBCs) in the body and a less than normal quantity of hemoglobin in the blood. CDA may be transmitted by both parents autosomal recessively or dominantly.
Ineffective erythropoiesis is active erythropoiesis with premature death of red blood cells, a decreased output of RBCs from the bone marrow, and, consequently, anemia. It is a condition characterised by the presence or abundance of dysfunctional progenitor cells.
Majeed syndrome is an inherited skin disorder characterized by chronic recurrent multifocal osteomyelitis, congenital dyserythropoietic anemia and a neutrophilic dermatosis. It is classified as an autoinflammatory bone disorder. The condition is found in people with two defective copies of the LPIN2 gene. LPIN2 encodes lipin-2 which is involved in lipid metabolism. The pathogenesis of this mutation with the clinical manifestations has not been elucidated.
Congenital dyserythropoietic anemia type I is a disorder of blood cell production, particularly of the production of erythroblasts, which are the precursors of the red blood cells (RBCs).
Congenital dyserythropoietic anemia type II, or hereditary erythroblastic multinuclearity with positive acidified serum lysis test (HEMPAS) is a rare genetic anemia in humans characterized by hereditary erythroblastic multinuclearity with positive acidified serum lysis test.
Congenital dyserythropoietic anemia type III is a rare autosomal dominant disorder characterized by macrocytic anemia, bone marrow erythroid hyperplasia and giant multinucleate erythroblasts. New evidence suggests that this may be passed on recessively as well.
The human CDAN1 gene encodes the protein Codanin 1.
A nucleated red blood cell (NRBC), also known by several other names, is a red blood cell that contains a cell nucleus. Almost all vertebrate organisms have hemoglobin-containing cells in their blood, and with the exception of mammals, all of these red blood cells are nucleated. In mammals, NRBCs occur in normal development as precursors to mature red blood cells in erythropoiesis, the process by which the body produces red blood cells. NRBCs are normally found in the bone marrow of humans of all ages and in the blood of fetuses and newborn infants. After infancy, RBCs normally contain a nucleus only during the very early stages of the cell's life, and the nucleus is ejected as a normal part of cellular differentiation before the cell is released into the bloodstream. Thus, if NRBCs are identified on an adult's complete blood count or peripheral blood smear, it suggests that there is a very high demand for the bone marrow to produce RBCs, and immature RBCs are being released into circulation. Possible pathologic causes include anemia, myelofibrosis, thalassemia, miliary tuberculosis, cancers involving bone marrow, and in chronic hypoxemia.
Dyserythropoiesis refers to the defective development of red blood cells, also called erythrocytes. This problem can be congenital, acquired, or inherited. Some red blood cells may be destroyed within the bone marrow during the maturation process, whereas others can enter the circulation with abnormalities. These abnormalities can be functional and/or morphological, which can lead to anemia since there may be increased turnover of red blood cells. There are a number of diseases that cause dyserythropoiesis. Congenital/inherited causes include congenital dyserythropoietic anemia, thalassemia, pyruvate kinase deficiency, hereditary pyropoikilocytosis, and abetalipoproteinemia. Acquired causes include nutrient deficiency/malnutrition, myelodysplasia, HIV infection, and certain medications.