Congenital dyserythropoietic anemia

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Congenital dyserythropoietic anemia
Other namesCDA [1]
Blausen 0761 RedBloodCells.png
CDA causes decrease in red blood cells.
Specialty Hematology   OOjs UI icon edit-ltr-progressive.svg
Symptoms Weakness [2]
TypesCDA Type I, CDA Type II, CDA Type III, and CDA Type IV [1]
Diagnostic method Genetic testing [3]
TreatmentBlood transfusions(also depends on which type) [4]

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. [2] CDA may be transmitted by both parents autosomal recessively or dominantly.[ citation needed ]

Contents

Chromosome 15 (KIF23) Human male karyotpe high resolution - Chromosome 15 cropped.png
Chromosome 15 (KIF23)

Types

Congenital dyserythropoietic anemia has four different subtypes, CDA Type I, CDA Type II, CDA Type III, and CDA Type IV. CDA type II (CDA II) is the most frequent type of congenital dyserythropoietic anemias.[ citation needed ]

TypeSymptomsBone marrow morphology OMIM GeneLocus
Type I
(CDAN1)		Moderate to severe macrocytic anemia (commonly in neonates as intrauterine growth retardation). [5] Erythroid precursors with incompletely divided erythroid cells held together with thin chromatin bridges. [6] Ia 224120 CDAN1 15q15
Ib 615631 C15ORF41 15q14
Type II
(CDAN2)		Moderate anemia, splenomegaly, and hepatomegaly. [7] Binucleate and rare multinucleate polychromatic erythroblasts. [6] 224100 SEC23B 20p11.2
Type III
(CDAN3)		Mild anemia and retinal degeneration. [7] Giant multinucleated erythroblasts. [6] 105600 KIF23 15q21
Type IV
(CDAN4)		Severe anemia at birth. [8] [9] 613673 KLF1 19p13.13-p13.12

Signs and symptoms

The symptoms and signs of congenital dyserythropoietic anemia are consistent with: [2]

Diagnosis

The diagnosis of congenital dyserythropoietic anemia can be done via sequence analysis of the entire coding region, types I, [10] II, [11] III [12] and IV ( is a relatively new form of CDA that had been found, just 4 cases have been reported [9] ) according to the genetic testing registry.[ citation needed ]

Treatment

Deferasirox Deferasirox ball-and-stick model.png
Deferasirox

Treatment of individuals with CDA usually consist of frequent blood transfusions, but this can vary depending on the type that the individual has. [4] Patients report going every 2–3 weeks for blood transfusions.[ citation needed ]

In addition, they must undertake chelation therapy to survive; [13] either deferoxamine, deferasirox, or deferiprone to eliminate the excess iron that accumulates. [14] Removal of the spleen [15] and gallbladder [16] are common. Hemoglobin levels can run anywhere between 8.0 g/dl and 11.0 g/dl in untransfused patients, the amount of blood received by the patient is not as important as their baseline pre-transfusion hemoglobin level. [17] This is true for ferritin levels and iron levels in the organs as well, it is important for patients to go regularly for transfusions in order to maximize good health, normal ferritin levels run anywhere between 24 and 336 ng/ml, [18] hematologists generally do not begin chelation therapy until ferritin levels reach at least 1000 ng/ml. [19] It is more important to check iron levels in the organs through MRI scans, 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. [14]

Gene therapy

Gene therapy, as well as, bone marrow transplant are also possible treatments for the disorder, but each have their own risks at this point in time. Bone marrow transplantation is the more used method between the two, whereas researchers are still trying to definitively establish the results of gene therapy treatment. 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 an alternative.[ medical citation needed ]

CDA at both clinical and genetic aspects are part of a heterogeneous group of genetic conditions. Gene therapy is still experimental and has largely only been tested in animal models until now. This type of therapy has promise, 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). [16] [20]

In the United States, the FDA approved clinical trials on Beta thalassemia patients in 2012. The first study, which took place in July 2012, recruited human subjects with thalassemia major, [21]

See also

Related Research Articles

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<span class="mw-page-title-main">Thalassemia</span> Family of inherited blood disorders

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<span class="mw-page-title-main">Microcytic anemia</span> Medical condition

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<span class="mw-page-title-main">Hypochondroplasia</span> Medical condition

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<span class="mw-page-title-main">Alpha-thalassemia</span> Thalassemia involving the genes HBA1and HBA2 hemoglobin genes

Alpha-thalassemia is a form of thalassemia involving the genes HBA1 and HBA2. Thalassemias are a group of inherited blood conditions which result in the impaired production of hemoglobin, the molecule that carries oxygen in the blood. Normal hemoglobin consists of two alpha chains and two beta chains; in alpha-thalassemia, there is a quantitative decrease in the amount of alpha chains, resulting in fewer normal hemoglobin molecules. Furthermore, alpha-thalassemia leads to the production of unstable beta globin molecules which cause increased red blood cell destruction. The degree of impairment is based on which clinical phenotype is present.

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<span class="mw-page-title-main">Beta thalassemia</span> Blood disorder

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.

<span class="mw-page-title-main">Chronic mucocutaneous candidiasis</span> Medical condition

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Congenital hemolytic anemia (CHA) is a diverse group of rare hereditary conditions marked by decreased life expectancy and premature removal of erythrocytes from blood flow. Defects in erythrocyte membrane proteins and red cell enzyme metabolism, as well as changes at the level of erythrocyte precursors, lead to impaired bone marrow erythropoiesis. CAH is distinguished by variable anemia, chronic extravascular hemolysis, decreased erythrocyte life span, splenomegaly, jaundice, biliary lithiasis, and iron overload. Immune-mediated mechanisms may play a role in the pathogenesis of these uncommon diseases, despite the paucity of data regarding the immune system's involvement in CHAs.

Congenital hypoplastic anemia is a congenital disorder that occasionally also includes leukopenia and thrombocytopenia and is characterized by deficiencies of red cell precursors.

<span class="mw-page-title-main">Majeed syndrome</span> Medical condition

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.

Congenital dyserythropoietic anemia type IV has been described with typical morphologic features of CDA II but a negative acidified-serum test.

Treatment of the inherited blood disorder thalassemia depends upon the level of severity. For mild forms of the condition, advice and counseling are often all that are necessary. For more severe forms, treatment may consist in blood transfusion; chelation therapy to reverse iron overload, using drugs such as deferoxamine, deferiprone, or deferasirox; medication with the antioxidant indicaxanthin to prevent the breakdown of hemoglobin; or a bone marrow transplant using material from a compatible donor, or from the patient's mother. Removal of the spleen (splenectomy) could theoretically help to reduce the need for blood transfusions in people with thalassaemia major or intermedia but there is currently no reliable evidence from clinical trials about its effects. Population screening has had some success as a preventive measure.

<span class="mw-page-title-main">Transfusion-dependent anemia</span>

Transfusion-dependent anemia is a form of anemia characterized by the need for continuous blood transfusion. It is a condition that results from various diseases, and is associated with decreased survival rates. Regular transfusion is required to reduce the symptoms of anemia by increasing functional red blood cells and hemoglobin count. Symptoms may vary based on the severity of the condition and the most common symptom is fatigue. Various diseases can lead to transfusion-dependent anemia, most notably myelodysplastic syndromes (MDS) and thalassemia. Due to the number of diseases that can cause transfusion-dependent anemia, diagnosing it is more complicated. Transfusion dependence occurs when an average of more than 2 units of blood transfused every 28 days is required over a period of at least 3 months. Myelodysplastic syndromes is often only diagnosed when patients become anemic, and transfusion-dependent thalassemia is diagnosed based on gene mutations. Screening for heterozygosity in the thalassemia gene is an option for early detection.

Hemolytic jaundice, also known as prehepatic jaundice, is a type of jaundice arising from hemolysis or excessive destruction of red blood cells, when the byproduct bilirubin is not excreted by the hepatic cells quickly enough. Unless the patient is concurrently affected by hepatic dysfunctions or is experiencing hepatocellular damage, the liver does not contribute to this type of jaundice.

References

  1. 1 2 RESERVED, INSERM US14 -- ALL RIGHTS. "Orphanet: Congenital dyserythropoietic anemia". www.orpha.net. Archived from the original on 3 January 2018. Retrieved 2 January 2018.{{cite web}}: CS1 maint: numeric names: authors list (link)
  2. 1 2 3 "CDA". Genetics Home Reference. 2016-01-25. Archived from the original on 2018-01-02. Retrieved 2016-01-29.
  3. ↑ "Congenital dyserythropoietic anemia - Conditions - GTR - NCBI". www.ncbi.nlm.nih.gov. Archived from the original on 27 May 2018. Retrieved 2 January 2018.
  4. 1 2 Greer, John P.; Arber, Daniel A.; Glader, Bertil; List, Alan F.; Means, Robert T.; Paraskevas, Frixos; Rodgers, George M. (2013-08-29). Wintrobe's Clinical Hematology. Lippincott Williams & Wilkins. p. 994. ISBN   9781469846224.
  5. ↑ Tamary, Hannah; Dgany, Orly (1993-01-01). Pagon, Roberta A.; Adam, Margaret P.; Ardinger, Holly H.; Wallace, Stephanie E.; Amemiya, Anne; Bean, Lora J.H.; Bird, Thomas D.; Fong, Chin-To; Mefford, Heather C. (eds.). Congenital Dyserythropoietic Anemia Type I. Seattle (WA): University of Washington, Seattle. PMID   20301759. Archived from the original on 2019-12-17. Retrieved 2017-08-30.
  6. 1 2 3 Iolascon A, Esposito MR, Russo R (2012). "Clinical aspects and pathogenesis of congenital dyserythropoietic anemias: from morphology to molecular approach". Haematologica. 97 (12): 1786–94. doi:10.3324/haematol.2012.072207. PMC   3590084 . PMID   23065504.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  7. 1 2 Delaunay, Jean (2003). "Congenital dyserythropoietic anemia" (PDF). Orpha.net. Orphanet. Archived from the original (PDF) on 13 August 2017. Retrieved 29 January 2016.
  8. ↑ Lanzkowsky, Philip (2005-06-06). Manual of Pediatric Hematology and Oncology. Academic Press. p. 159. ISBN   9780123751553.
  9. 1 2 RESERVED, INSERM US14 -- ALL RIGHTS. "Orphanet: Congenital dyserythropoietic anemia type IV". www.orpha.net. Archived from the original on 2017-12-13. Retrieved 2016-01-29.{{cite web}}: CS1 maint: numeric names: authors list (link)
  10. ↑ "Congenital dyserythropoietic anemia, type I - Conditions - GTR - NCBI". www.ncbi.nlm.nih.gov. Archived from the original on 2017-06-15. Retrieved 2016-01-29.
  11. ↑ "Congenital dyserythropoietic anemia, type II - Conditions - GTR - NCBI". www.ncbi.nlm.nih.gov. Archived from the original on 2017-06-15. Retrieved 2016-01-29.
  12. ↑ "Congenital dyserythropoietic anemia, type III - Conditions - GTR - NCBI". www.ncbi.nlm.nih.gov. Archived from the original on 2017-06-15. Retrieved 2016-01-29.
  13. ↑ "Congenital dyserythropoietic anemia type 2 | Disease | Treatment | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Archived from the original on 2016-02-05. Retrieved 2016-01-29.
  14. 1 2 "Iron Overload. Medical information about Iron Overload | Patient". Patient. Archived from the original on 2019-05-24. Retrieved 2016-01-29.
  15. ↑ Heimpel, Hermann; Anselstetter, Volker; Chrobak, Ladislav; Denecke, Jonas; Einsiedler, Beate; Gallmeier, Kerstin; Griesshammer, Antje; Marquardt, Thorsten; Janka-Schaub, Gritta (2003-12-15). "Congenital dyserythropoietic anemia type II: epidemiology, clinical appearance, and prognosis based on long-term observation". Blood. 102 (13): 4576–4581. doi:10.1182/blood-2003-02-0613. ISSN   0006-4971. PMID   12933587. S2CID   1553686.
  16. 1 2 Iolascon, A.; Esposito, M. R.; Russo, R. (2012-12-01). "Clinical aspects and pathogenesis of congenital dyserythropoietic anemias: from morphology to molecular approach". Haematologica. 97 (12): 1786–1794. doi:10.3324/haematol.2012.072207. PMC   3590084 . PMID   23065504.
  17. ↑ Denecke, Jonas; Marquardt, Thorsten (2009-09-01). "Congenital dyserythropoietic anemia type II (CDAII/HEMPAS): Where are we now?" (PDF). Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. Genetic Glycosylation Diseases. 1792 (9): 915–920. doi:10.1016/j.bbadis.2008.12.005. PMID   19150496. S2CID   5639545. Archived (PDF) from the original on 2019-09-02. Retrieved 2019-09-02.
  18. ↑ "Ferritin: Reference Range, Interpretation, Collection and Panels". 2018-07-05. Archived from the original on 2016-03-05. Retrieved 2016-01-29.
  19. ↑ "Monitoring Treatment | Treatment and Management | Training & Education | Hemochromatosis (Iron Storage Disease) | NCBDDD | CDC". www.cdc.gov. Archived from the original on 2016-01-15. Retrieved 2016-01-29.
  20. ↑ "Gene Therapy is 'Becoming a Clinical Reality'". Archived from the original on 2015-12-26. Retrieved 2016-01-29.
  21. ↑ "Launch of Stem Cell Therapy Trial Offers Hope for Patients with Inherited Blood Disorder". 16 July 2012. Archived from the original on 8 June 2020. Retrieved 29 July 2012.

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