Congenital dyserythropoietic anemia: Difference between revisions
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{{SK}} CDA, dyserythropoiesis | |||
==Overview== | ==Overview== | ||
'''Congenital dyserythropoietic anemia''' (CDA) is a rare blood disorder, similar to the [[thalassemia]]s. 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.<ref>http://ghr.nlm.nih.gov/condition/congenital-dyserythropoietic-anemia</ref> | |||
==Historical Perspective== | |||
==Classification== | |||
==Pathophysiology== | |||
== | ==Causes== | ||
CDA is transmitted by both parents autosomal recessively (although CDA type III appears to have an autosomal dominant pattern of inheritance<ref>http://ghr.nlm.nih.gov/condition/congenital-dyserythropoietic-anemia</ref>) 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.<ref>http://bloodjournal.hematologylibrary.org/cgi/content/abstract/102/13/4576</ref> | CDA is transmitted by both parents autosomal recessively (although CDA type III appears to have an autosomal dominant pattern of inheritance<ref>http://ghr.nlm.nih.gov/condition/congenital-dyserythropoietic-anemia</ref>) 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.<ref>http://bloodjournal.hematologylibrary.org/cgi/content/abstract/102/13/4576</ref> | ||
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| 19p13.13-p13.12 | | 19p13.13-p13.12 | ||
|} | |} | ||
==Differentiating {{PAGENAME}} from Other Diseases== | |||
==Epidemiology and Demographics== | |||
==Risk Factors== | |||
==Screening== | |||
==Natural History, Complications, and Prognosis== | |||
===Natural History=== | |||
===Complications=== | |||
===Prognosis=== | |||
==Diagnosis== | |||
===Diagnostic Criteria=== | |||
===History and Symptoms=== | |||
===Physical Examination=== | |||
===Laboratory Findings=== | |||
===Imaging Findings=== | |||
===Other Diagnostic Studies=== | |||
==Treatment== | ==Treatment== | ||
===Medical Therapy=== | |||
Patients with CDA typically get frequent [[blood transfusion]]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. | Patients with CDA typically get frequent [[blood transfusion]]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.<ref>http://www.medscape.com/viewarticle/751573</ref> 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). | 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.<ref>http://www.medscape.com/viewarticle/751573</ref> 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). | ||
[[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.<ref>http://www.medscape.com/viewarticle/728656</ref> A second trial on another patient in France is due to occur sometime by the year 2016.<ref>http://www.youtube.com/watch?v=eix2m1KDHS4</ref> 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.<ref>http://www.mskcc.org/blog/launch-stem-cell-therapy-trial-offers-hope-patients-inherited-blood-disorder</ref> The study is set to end in 2014.<ref>http://clinicaltrials.gov/ct2/show/NCT01639690?term=lentiviral+thalassemia&rank=1</ref> | [[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.<ref>http://www.medscape.com/viewarticle/728656</ref> A second trial on another patient in France is due to occur sometime by the year 2016.<ref>http://www.youtube.com/watch?v=eix2m1KDHS4</ref> 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.<ref>http://www.mskcc.org/blog/launch-stem-cell-therapy-trial-offers-hope-patients-inherited-blood-disorder</ref> The study is set to end in 2014.<ref>http://clinicaltrials.gov/ct2/show/NCT01639690?term=lentiviral+thalassemia&rank=1</ref> | ||
===Surgery=== | |||
===Prevention=== | |||
==Related Chapters== | ==Related Chapters== | ||
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* [http://ghr.nlm.nih.gov/condition=congenitaldyserythropoieticanemia Congenital dyserythropoietic anemia] at the US [[National Institutes of Health]] Home Genetic Reference | * [http://ghr.nlm.nih.gov/condition=congenitaldyserythropoieticanemia Congenital dyserythropoietic anemia] at the US [[National Institutes of Health]] Home Genetic Reference | ||
[[Category: | [[Category:Hematology]] | ||
Latest revision as of 19:15, 20 June 2016
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Synonyms and keywords: CDA, dyserythropoiesis
Overview
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.[1]
Historical Perspective
Classification
Pathophysiology
Causes
CDA is transmitted by both parents autosomal recessively (although CDA type III appears to have an autosomal dominant pattern of inheritance[2]) 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.[3]
Types include:
| Type | OMIM | Gene | Locus |
|---|---|---|---|
| CDAN1 | 224120 | CDAN1 | 15q15 |
| CDAN2 | 224100 | SEC23B | 20p11.2 |
| CDAN3 | 105600 | CDAN3 | 15q21 |
| CDAN4 | 613673 | KLF1 | 19p13.13-p13.12 |
Differentiating Congenital dyserythropoietic anemia from Other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications, and Prognosis
Natural History
Complications
Prognosis
Diagnosis
Diagnostic Criteria
History and Symptoms
Physical Examination
Laboratory Findings
Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy
Patients with CDA typically get frequent blood transfusions, 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.[4] 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).
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.[5] A second trial on another patient in France is due to occur sometime by the year 2016.[6] 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.[7] The study is set to end in 2014.[8]
Surgery
Prevention
Related Chapters
References
- ↑ http://ghr.nlm.nih.gov/condition/congenital-dyserythropoietic-anemia
- ↑ http://ghr.nlm.nih.gov/condition/congenital-dyserythropoietic-anemia
- ↑ http://bloodjournal.hematologylibrary.org/cgi/content/abstract/102/13/4576
- ↑ http://www.medscape.com/viewarticle/751573
- ↑ http://www.medscape.com/viewarticle/728656
- ↑ http://www.youtube.com/watch?v=eix2m1KDHS4
- ↑ http://www.mskcc.org/blog/launch-stem-cell-therapy-trial-offers-hope-patients-inherited-blood-disorder
- ↑ http://clinicaltrials.gov/ct2/show/NCT01639690?term=lentiviral+thalassemia&rank=1
External links
- Delaunay entry on Congenital Dyserythropoietic Anemia
- Congenital dyserythropoietic anemia at the US National Institutes of Health Home Genetic Reference