Congenital dyserythropoietic anemia type I (CDA-I) is a rare
genetic disease that affects erythropoiesis. On the other hand,
hemoglobin H (HbH) disease is a severe form of
alpha-thalassemia. We herein present ultrastructural and immunocytochemical data concerning the first reported case of congenital
anemia with clinical and molecular diagnosis of HbH disease complicated by CDA-I-specific dysplasies of the erythroid cells. Fine structure and transmission electron microscope immunolabeling analysis of the bone marrow and peripheral blood samples were consistent with a potential co-existence of the two defects in the same patient, producing a novel and diagnostically important dyserythropoietic profile. In the patient under investigation both nuclear and plasma membrane of the erythroid cells are almost equally defective. The unknown defect causes the concomitant precipitation of beta- and
alpha-globin chains (or
hemoglobin), along with an unidentified
protein(s). The unusual inclusions gain access to the
euchromatin area and exhibit higher affinity for the plasma membrane than the classic inclusions of precipitated alpha- or
beta-globin chains seen in
thalassemia. The affected erythroid precursors are presented with severe nuclear distortions, endonuclear
globin loads, morphological evidence of apoptosis and increased erythrophagocytosis. Plasma membrane distortions and the rate of
protein precipitation were aggravated with differentiation. Our findings provide additional evidence for a specific activation of a beta-thalassemic-like mechanism in CDA-I, containing not only the
hemoglobin biosynthesis as previously suggested, and interpret the prototypal hematological portrait, which is an HbH disease, modified and partially counterbalanced by the effect of CDA-I or an unidentified CDA-I-like disease. The reported data describe the complexity of the interactions between the CDA-I and the HbH disease, revealing essential pathogenic events of the novel
anemia and, indirectly, of the CDA-I.