The Ultrastructure of Erythroblasts in a Case of Congenital Anemia with Features of both β-Thalassemia and Congenital Dyserythropoietic Anemia Type I (CDA-I)

Abstract

INTRODUCTION: β-Thalassemia is a relatively rare congenital disorder characterized by hemolysis and ineffective erythropoiesis due to impaired synthesis of globin β-chain, while CDAs are other types of rare disorders defined by peculiar nuclear abnormality of erythroblasts. We experienced an interesting case with features of both β-thalassemia and CDA-I.
CASE REPORT: A 27-yr old male was referred to Tenri Hospital for the evaluation of anemia. He was diagnosed as having “aplastic anemia” at 4 yr of age. At 20 yr of age, the patient was diagnosed as having β-thalassemia. His liver and spleen were enlarged and each was palpable 3 cm below the costal margin. The hematological findings were as follows: Hb 4.2g/dl, Retics 0.8%, PLT 9.9×10⁴/cu mm, WBC 2100/cu mm. The red cell morphology showed anisopoikilocytosis, anisochromia, tear drop cells, leptocytes and target cells. Bone marrow examination revealed hyperplasia of erythroid precursors with megaloblastoid change and multinuclearity. Anisocytosis and abnormal nuclear segmentation were observed in megakaryocytes, and imbalanced maturation of nucleus and cytoplasm in myeloid precursors. Blood chemistry showed normal range of serum VB₁₂, VB₆ and folic acid. CFU-GM and CFU-E were also within normal range. Ferrokinetic study showed shortened PIDT1/2, enhanced PIT and markedly reduced % RCU. Half life of ⁵¹Cr-labeled RBC was shortened (14.9 d). The data described above indicate that the cause of the patient's anemia was a combination of ineffective erythropoiesis and hemolysis. No abnormal Hb was observed, although Hb F (2,3%) and Hb A₂ (5.3%) were increased The ratio of β-chain synthesis to α-chain synthesis was 0.58, indicating that this case was the heterozygote of β-thalassemia. Electron microscopic study showed various morphological abnormalities of bone marrow erythroblasts; partial loss of nuclear membrane, spongy and donut-like apperrance of heterochromatin, and nuclear clefts (CDA-I); aggregated dense granules in the nucleus and loop-like protrusion of the cytoplasm (thalassemia); iron-laden mitochondria and autophagolysosomes (both CDA-I & thalassemia).
DISCUSSION: Unexpectedly severe anemia in this heterozygous thalassemia patient probably resulted from the complication of CDA-like nuclear abnormalities Ultrastructural study of erythroblasts in anemic patients of unknown cause may be helpful in revealing the cause of anemia.