Congenital dyserythropoietic anemia
|Congenital dyserythropoietic anemia|
|Classification and external resources|
|NCI||Congenital dyserythropoietic anemia|
|Patient UK||Congenital dyserythropoietic anemia|
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.
CDA may be transmitted by both parents autosomal recessively or dominantly 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.
Patients with CDA typically get frequent blood transfusions, but this can vary depending on the type that is acquired. Patients report going every 2–4 weeks for blood transfusions, and receive somewhere between 1-2 adult units of blood (1-2 child units for children). In addition, they must undertake chelation therapy to survive; either deferoxamine (i.e. Desferal), deferasirox (i.e. Exjade, Asunra), 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 can run anywhere between 6.0 g/dl and 8.0 g/dl in untransfused patients, and between 9.0 g/dl and 13.0 g/dl in well transfused patients. It should be noted that the amount of blood received by the patient is not as important as their baseline pre-transfusion hemoglobin level. The closer the patient is to the normal range, the better he or she will feel. This is true for ferritin levels and iron levels in the organs as well. It is important for patients 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, has also recently been 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 a trend, and do not reflect actual organ iron content.
Bone marrow transplant and gene therapy are the only known cures for the disorder, but each have their own risks at this point in time. Bone marrow transplantation is the more established cure, as it has been proven to work in human subjects, whereas researchers are still trying to definitively establish this with gene therapy. It generally requires a 10/10 HLA matched donor, however, who is usually a sibling. As most patients do not have this, they must rely on gene therapy research to potentially provide them with a cure. Gene therapy is still experimental and has largely only been tested in animal models until now. This type of 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. In the United States, the FDA approved clinical trials on Beta thalassemia patients in 2012. The first study, which takes place at Memorial Sloan Kettering Cancer Center in New York, has begun recruiting human subjects with thalassemia major in July 2012. The study is set to end in 2014.