Very rare. Heterogeneous group of hematological disorders (erythrocyte abnormalities and especially anemia) related to a mutation of a gene regulating the proliferation, division or maturation of young red blood cells of the bone marrow (erythroblasts). The first signs usually appear during childhood or early adulthood, although some clinical signs may occasionally be observed during the neonatal period: chronic anemia of varying severity and jaundice, frequently associated with splenomegaly and/or hepatomegaly. Erythropoiesis is always dysfunctional, as revealed by cellular abnormalities and erythroid hyperplasia at bone marrow biopsy.

Five types were identified: I, II, III, IV and thrombocytopenia with congenital dyserythropoietic anemia.

-        type Ia [MIM 224 120]: autosomal recessive transmission of mutations of the CDAN1 gene (15q15.2), coding for codanine or, type Ib, the C15ORF41 gene (15q14) [MIM 615 631] coding for an endonuclease possibly involved in the DNA replication and/or the chromatin assembly. Moderate macrocytic anemia with frequent splenomegaly. Swiss cheese - shaped erythroblasts. Jaundice is intermittent and about 1/3 of the patients have congenital malformations, mostly involving the limbs (and scoliosis), but also the heart, kidneys or hip. The main complication is iron overload.

-        type II (most common form) [MIM 224 100]: autosomal recessive transmission of mutations of the SEC23B gene (20p11.23) coding for a  protein of the mantle involved in the exchanges between the reticulum and the Golgi apparatus. Anemia and/or jaundice is usually accompanied by splenomegaly in children or young adults. Hepatic iron overload and gallstones are common.

-        type IIIa (very rare) [MIM 105 600]: autosomal dominant transmission of mutations of the KIF23 gene (15q23) coding for a mitotic kinesin (MKLP1), crucial for cytokinesis. Moderate hemolytic anemia and predisposition to angioid streaks, gammopathies and myeloma. Giant multinucleated erythroblasts. Type IIIb [MIM 619 789] autosomal recessive transmission of mutations of the RACGAP1 gene  (12q13).

-        type IV [MIM 613 673]: autosomal dominant transmission of mutations of the erythroid transcription factor gene KLF1 (19p13.2). Presence of a very large number of nucleated erythrocytes in the peripheral blood. High fetal hemoglobin level.

-        type V: X-linked transmission of mutations of the erythroid transcription factor gene GATA1 (Xp11.23). Dysmorphic erythrocytes and platelet deficiency.

Anesthetic implications: 

check hemoglobin levels; check blood iron and the absence of hemochromatosis sequelae (see this term).

References : 

-        Gambale A, Iolascon A, Andolfo I, Russo R.
Diagnosis and management of congenital dyserythropoietic anemias.
Expert Rev Hematol 2016; 9 :283-96.

Updated: July 2022