AN ALPHA-THALASSEMIC HEMOGLOBINOPATHY - HOMOZYGOSITY FOR THE HB AGRINIO ALPHA-2-GLOBIN CHAIN VARIANT

This report describes the first case of homozygosity for the Hb Agrini o [alpha 29(B10)Leu-->Pro] alpha 2-globin gene variant (codon 29, C (T ) under bar G-->C (C) under bar G) in a Greek patient. At 12 months of age, the proband presented with a marked hypochromic, microcytic anem ia, a very low level of Hb H (<2.5%), rare Hb H inclusions, and a bala nced alpha/non-alpha biosynthesis ratio. The mother had hematological findings and globin biosynthesis consistent with heterozygous beta-tha lassemia, but paradoxically, red cell morphology demonstrated very rar e Hb H inclusions. The father had mild microcytosis and hypochromia. A nalysis of alpha- and beta-globin genotypes demonstrated that the pati ent was homozygous for the highly unstable Hb Agrinio variant, caused by a T-->C mutation in codon 29 of the alpha 2-globin gene. At the age of 13 years, the proband had a clinical phenotype compatible with mil d thalassemia intermedia with moderate anemia (Hb 7-8 g/dL), normal gr owth and development, slight splenomegaly, and minimal bone changes, w hile Hb H and inclusion bodies were not detected.