Congenital dyserythropoietic anemia
Encyclopedia
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. This shortage prevents the blood from carrying an adequate supply of oxygen to the body's tissues, resulting in various symptoms of anemia including: tiredness (fatigue), weakness, pale skin, and other similar complications.
Types include:
s, but this can vary depending on the type that is acquired. Patients report going every 3–5 weeks for blood transfusions, and receive somewhere between 1-2 adult units of blood (3-4 child units for children). In addition, they must undertake chelation therapy to survive; either deferoxamine
(i.e . Desferal), deferasirox
(i.e. Exjade), or deferiprone
(i.e. Kelfer, Ferriprox, L1) to eliminate the excess iron that accumulates. In a clinical sense, the disorder is very similar to thalassemia major (Beta-thalassemia
) and treated in the same fashion. Removal of the spleen and gallbladder are common, and problems with the liver and heart become increasingly important as the individual ages, due to stresses from low hemoglobin counts and high iron content. Hemoglobin levels usually run anywhere between 6.0 gm/dl and 7.0 gm/dl in untransfused patients, and between 8.0 gm/dl and 10.0 gm/dl in well transfused patients. It is important to go regularly for transfusions and to chelate daily in order to maximize good health.
Exjade, an oral chelator approved by the FDA in November 2005, has made chelation therapy much easier for patients, who previously could only chelate subcutaneously. Deferiprone, another oral chelator, was also recently approved by the FDA on October 14, 2011. While normal ferritin levels run anywhere between 24 and 336 ng/ml, hematologists generally do not begin chelation therapy until ferritin levels reach at least 1000 ng/ml. It is more important to check iron levels in the organs through annual MRI scans (T2* for the heart, R2 for the liver), however, than to simply get regular blood tests to check ferritin levels (which only show you a trend, and do not reflect actual organ iron content).
and gene therapy
are the only known cures for the disorder, but each have their own risks at this point in time. Gene therapy is especially promising, however, as it allows for the autologous transplantation of the patient's own healthy stem cells rather than requiring an outside donor, thereby bypassing any potential for graft vs. host disease (GVHD). Clinical trials on one 18 year old boy in France in 2007 have suggested that he is cured of Beta-thalassemia three years later with no complications noted so far. A second trial on another patient in France is due to occur sometime by the year 2016.
Anemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
, characterized by ineffective erythropoiesis
Ineffective erythropoiesis
Ineffective erythropoiesis a kinetic term that describes active erythropoiesis with premature death of red blood cells, a decreased output of RBCs from the bone marrow, and, consequently, anemia....
, 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. This shortage prevents the blood from carrying an adequate supply of oxygen to the body's tissues, resulting in various symptoms of anemia including: tiredness (fatigue), weakness, pale skin, and other similar complications.
Genetics
CDA is transmitted by both parents autosomal recessively (although CDA type III appears to have an autosomal dominant pattern of inheritance) and has over four different subtypes, but CDA Type I, CDA Type II, CDA Type III, and CDA Type IV are the most common. CDA type II (CDA II) is the most frequent type of congenital dyserythropoietic anemias. More than 200 cases have been described, but with the exception of a report by the International CDA II Registry, these reports include only small numbers of cases and no data on the lifetime evolution of the disease.Types include:
| Type | OMIM | Gene | Locus |
|---|---|---|---|
| CDAN1 | CDAN1 | 15q15 | |
| CDAN2 | SEC23B SEC23B Protein transport protein Sec23B is a protein that in humans is encoded by the SEC23B gene.-Further reading:... |
20p11.2 | |
| CDAN3 | CDAN3 | 15q21 | |
| CDAN4 | KLF1 | 19p13.13-p13.12 |
Treatment
Patients with CDA typically get frequent blood transfusionBlood transfusion
Blood transfusion is the process of receiving blood products into one's circulation intravenously. Transfusions are used in a variety of medical conditions to replace lost components of the blood...
s, but this can vary depending on the type that is acquired. Patients report going every 3–5 weeks for blood transfusions, and receive somewhere between 1-2 adult units of blood (3-4 child units for children). In addition, they must undertake chelation therapy to survive; either deferoxamine
Deferoxamine
Deferoxamine is a bacterial siderophore produced by the actinobacteria Streptomyces pilosus. It has medical applications as a chelating agent used to remove excess iron from the body...
(i.e . Desferal), deferasirox
Deferasirox
Deferasirox is a rationally-designed oral iron chelator. Its main use is to reduce chronic iron overload in patients who are receiving long-term blood transfusions for conditions such as beta-thalassemia and other chronic anemias...
(i.e. Exjade), or deferiprone
Deferiprone
Deferiprone is an oral drug that chelates iron and is used to treat thalassaemia major.It has been licensed for use in Europe and Asia for many years while awaiting approval in Canada and the United States. On October 14, 2011, however, "the U.S...
(i.e. Kelfer, Ferriprox, L1) to eliminate the excess iron that accumulates. In a clinical sense, the disorder is very similar to thalassemia major (Beta-thalassemia
Beta-thalassemia
Beta-thalassemias are a group of inherited blood disorders caused by reduced or absent synthesis of the beta chains of hemoglobin resulting in variable phenotypes ranging from severe anemia to clinically asymptomatic individuals. The total annual incidence of symptomatic individuals is estimated...
) and treated in the same fashion. Removal of the spleen and gallbladder are common, and problems with the liver and heart become increasingly important as the individual ages, due to stresses from low hemoglobin counts and high iron content. Hemoglobin levels usually run anywhere between 6.0 gm/dl and 7.0 gm/dl in untransfused patients, and between 8.0 gm/dl and 10.0 gm/dl in well transfused patients. It is important to go regularly for transfusions and to chelate daily in order to maximize good health.
Exjade, an oral chelator approved by the FDA in November 2005, has made chelation therapy much easier for patients, who previously could only chelate subcutaneously. Deferiprone, another oral chelator, was also recently approved by the FDA on October 14, 2011. While normal ferritin levels run anywhere between 24 and 336 ng/ml, hematologists generally do not begin chelation therapy until ferritin levels reach at least 1000 ng/ml. It is more important to check iron levels in the organs through annual MRI scans (T2* for the heart, R2 for the liver), however, than to simply get regular blood tests to check ferritin levels (which only show you a trend, and do not reflect actual organ iron content).
Curative Options
Bone marrow transplantBone marrow transplant
Hematopoietic stem cell transplantation is the transplantation of multipotent hematopoietic stem cell or blood, usually derived from bone marrow, peripheral blood stem cells, or umbilical cord blood...
and gene therapy
Gene therapy
Gene therapy is the insertion, alteration, or removal of genes within an individual's cells and biological tissues to treat disease. It is a technique for correcting defective genes that are responsible for disease development...
are the only known cures for the disorder, but each have their own risks at this point in time. Gene therapy is especially promising, however, as it allows for the autologous transplantation of the patient's own healthy stem cells rather than requiring an outside donor, thereby bypassing any potential for graft vs. host disease (GVHD). Clinical trials on one 18 year old boy in France in 2007 have suggested that he is cured of Beta-thalassemia three years later with no complications noted so far. A second trial on another patient in France is due to occur sometime by the year 2016.
External links
- Delaunay entry on Congenital Dyserythropoietic Anemia
- Congenital dyserythropoietic anemia at the US National Institutes of HealthNational Institutes of HealthThe National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...
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