An α-Thalassemic Hemoglobinopathy: Homozygosity for the Hb Agrinio α2-Globin Chain Variant

Abstract

This report describes the first case of homozygosity for the Hb Agrinio [α29(B10)Leu-Pro] α2-globin gene variant (codon 29, CTG←CCG) in a Greek patient. At 12 months of age, the proband presented with a marked hypochromic, microcytic anemia, a very low level of Hb H (< 2.5%), rare Hb H inclusions, and a balanced α/non-α biosynthesis ratio. The mother had hematological findings and globin biosynthesis consistent with heterozygous β-thalassemia, but paradoxically, red cell morphology demonstrated very rare Hb H inclusions. The father had mild microcytosis and hypochromia. Analysis of α- and β-globin genotypes demonstrated that the patient was homozygous for the highly unstable Hb Agrinio variant, caused by a T-C mutation in codon 29 of the α2-globin gene. At the age of 13 years, the proband had a clinical phenotype compatible with mild thalassemia intermedia with moderate anemia (Hb 7–8 g/dL), normal growth and development, slight splenomegaly, and minimal bone changes, while Hb H and inclusion bodies were not detected.