Table 2.

Congenital Anemias of Interest in the Differential Diagnosis of Congenital Dyserythropoietic Anemia Type I

GeneDiffDx DisorderMOIClinical Features of DiffDx DisorderComment/Distinguishing Features
KIF23 1CDA IIIADRarest CDA. The most marked anomaly in bone marrow is the presence of giant multinucleated erythroblasts w/≤12 nuclei per cell. Addl findings incl retinal angioid streaks, macular degeneration, & monoclonal gammopathy ± multiple myeloma.The clinical presentation is similar to that of CDA I & CDA II; however, in the reported Swedish family, the anemia is not severe & transfusions are not required.
KLF1 CDA IV (OMIM 613673)ADAnemia of variable severity (intrauterine anemia & transfusion dependency to mild anemia). Splenomegaly is common. Peripheral blood w/↑ nucleated RBCs & bi-nucleated RBCs. MCV is usually nl. Reticulocytes usually lower compared to degree of anemia. HbF can be very high (≤40%), RBC CD44 is low.CDA IV has numerous nucleated RBCs on blood smear, MCV is not ↑, HbF is very high, BM EM shows erythroblasts w/cytoplasmic inclusions.
SEC23B CDA II (HEMPAS) (OMIM 224100) 2ARMost common CDA, characterized by mild-to-severe anemia, jaundice, & (in 50%-60% of affected persons) splenomegaly. ≤15% are transfusion dependent. 3 After age 20 yrs most develop iron overload.The diagnosis of CDA II requires evidence of congenital anemia, ineffective erythropoiesis, & typical bone marrow findings w/binuclearity in 10%-50% of erythroblasts.

AD = autosomal dominant; AR = autosomal recessive; BM = bone marrow; CDA = congenital dyserythropoietic anemia; DiffDx = differential diagnosis; EM = electron microscopy; HbF = fetal hemoglobin; MCV = mean corpuscular volume; MOI = mode of inheritance; RBC = red blood cell

1.
2.

CDA II is also known as HEMPAS (hereditary erythroblastic multinuclearity with positive acidified serum lysis test) because the RBCs of affected individuals are lysed by acidified sera of 40%-60% of healthy adults due to the presence of natural cold-reacting IgM antibody.

3.

From: Congenital Dyserythropoietic Anemia Type I

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