Congenital dyserythropoietic anemia type 3

Other Names: Dyserythropoietic anemia, congenital type 3; CDA III

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.

Cause

The genetic cause of CDA type III has not been identified. It likely results from mutations in a gene located on the long arm of chromosome 15 at a position designated 15q22. Researchers continue to search for the specific gene associated with this form of the condition. 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.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

In several families, CDA type III appears to have an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means that one copy of the altered gene in each cell is sufficient to cause the disorder. In these families, affected individuals often have a parent and other relatives with the condition.

Signs and symptoms

The signs and symptoms of CDA type III tend to be milder than those of the other types. Most affected individuals do not have hepatosplenomegaly, and iron does not build up in tissues and organs. In adulthood, abnormalities of a specialized tissue at the back of the eye (the retina) can cause vision impairment. Some people with CDA type III also have a blood disorder known as monoclonal gammopathy, which can lead to a cancer of white blood cells (multiple myeloma). of CDA type III tend to be milder than those of the other types. Most affected individuals do not have hepatosplenomegaly, and iron does not build up in tissues and organs. In adulthood, abnormalities of a specialized tissue at the back of the eye (the retina) can cause vision impairment. Some people with CDA type III also have a blood disorder known as monoclonal gammopathy, which can lead to a cancer of white blood cells (multiple myeloma).

Diagnosis

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.

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.

NIH genetic and rare disease info

• NIH info on Congenital dyserythropoietic anemia type 3

Congenital dyserythropoietic anemia type 3 is a rare disease.

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