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Congenital dyserythropoietic anemia type 3


Other Names:
Dyserythropoietic anemia, congenital type 3; CDA III
Categories:
The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 98870

Definition
Congenital dyserythropoietic anemia type III (CDA III) is a rare form of CDA (see this term) characterized by dyserythropoiesis, with big multinucleated erythroblasts in the bone marrow, and manifesting with mild to moderate anemia.

Epidemiology
The prevalence is unknown. Three families have been reported with autosomal dominant CDA III in Sweden, America and Argentina. Other sporadic CDA III-like cases have been described. In total, about 60 cases have been reported worldwide.

Clinical description
The clinical presentation is variable. CDA III can manifest with mild anemia and jaundice in neonates but it may not be discovered until childhood or adulthood. Intensity of symptoms increases during infections, following trauma, and during pregnancy. It can also be associated with monoclonal gammopathies, multiple myeloma (see this term) and retinal angioid streaks,which can lead to visual impairment. Sporadic cases of CDA III have been associated with severe erythroid hyperplasia, skeletal disorders, intellectual deficit, and hepatosplenomegaly.

Etiology
Recently, the KIF23 gene (15q23) has been identified as the causal mutation for AD CDA III. This gene encodes mitotic kinesin-like protein 1 (MKLP1) which is crucial for cytokinesis.

Diagnostic methods
Diagnosis is based on laboratory findings. The disorder is characterized by mild anemia, macrocytosis in the peripheral blood, and giant multinucleated erythroblasts (containing up to 12 nuclei) in the bone marrow. Increased levels of serum thymidine kinase, lactate dehydrogenase and bilirubin and very low or undetectable haptoglobin are also characteristic of this disease. Mutations in the KIF23 gene can also determine a diagnosis of CDA III.

Differential diagnosis
The diagnosis of CDA III should be considered following exclusion of other causes of macrocytosis (B12 deficiency, folic acid deficiency or other megaloblastic anemias such as pernicious anemia or thiamine-responsive megaloblastic anemia syndrome; see these terms), acquired dyserythropoiesis (myelodysplastic syndrome, acute erythroid leukemia), hemolytic anemias (hereditary spherocytosis) or microcytic anemias (thalassemias and iron deficiency anemias). Gilbert syndrome (see these terms) and infections should be also excluded.

Antenatal diagnosis
Prenatal diagnosis for at-risk pregnancies requires prior identification of the disease-causing mutations in the family.

Genetic counseling
Genetic counseling is possible in CDA III. It is inherited in an autosomal dominant mode. Other sporadic CDA III-like cases have been reported with an autosomal recessive pattern of inheritance, suggesting a different genetic alteration than KIF23 associated CDA III and possibly another subtype of CDA.

Management and treatment
In most cases anemia is mild and treatment is not necessary. Only during times of extreme anemia (often due to pregnancy or surgery), may a transfusion be needed. Ophthalmological follow-up is recommended in those with eye manifestations.

Prognosis
In most cases the prognosis is good and there is no decrease in life expectancy. Quality of life may be affected in those with visual impairment.

Visit the Orphanet disease page for more resources.
Last updated: 9/1/2013

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Anemia
Low number of red blood cells or hemoglobin
0001903
Anisocytosis
Unequal size of red blood cells
0011273
Poikilocytosis 0004447
30%-79% of people have these symptoms
Abnormal cellular phenotype 0025354
Abnormal proerythroblast morphology 0025035
Fatigue
Tired
Tiredness
[ more ] 		0012378
Hyperbilirubinemia
High blood bilirubin levels
0002904
Increased mean corpuscular volume 0005518
Increased serum iron 0003452
Increased total iron binding capacity 0025196
5%-29% of people have these symptoms
Elevated hepatic transaminase
High liver enzymes
0002910
Gingival bleeding
Bleeding gums
0000225
Headache
Headaches
0002315
Melena 0002249
Oral cavity bleeding
Bleeding from mouth
0030140
Pallor 0000980
Post-partum hemorrhage
Bleeding post-delivery
0011891
1%-4% of people have these symptoms
Short stature
Decreased body height
Small stature
[ more ] 		0004322
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance 0000006
Congenital hypoplastic anemia 0004810
Hemosiderinuria 0012543
Jaundice
Yellow skin
Yellowing of the skin
[ more ] 		0000952
Macrocytic anemia 0001972
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Last updated: 7/1/2020

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • The Centers for Mendelian Genomics program is working to discover the causes of rare genetic disorders. For more information about applying to the research study, please visit their website.

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on Congenital dyserythropoietic anemia type 3. This website is maintained by the National Library of Medicine.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.

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