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The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
Orpha Number: 98870
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.
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.
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.
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.
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.
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.
Prenatal diagnosis for at-risk pregnancies requires prior identification of the disease-causing mutations in the family.
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.
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.
Source: GARD Last updated on 05-01-20
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