Asymptomatic homozygous deletional β0‐thalassemia in an African individual

Homozygosity or compound heterozygosity for β0-thalassemia mutations most commonly results in a transfusion-dependent thalassemia major phenotype. In this report, we describe a 55-year-old male, from Guinea-Bissau, that had been asymptomatic and never transfused until being admitted to hospital with anemia, fever, splenomegaly, and asthenia. Following hospital admission, HIV-2 and Mycobacterium tuberculosis infections were diagnosed, and biochemical and molecular studies revealed homozygosity for β0-thalassemia. At the molecular level, this is the first description of homozygosity for the β0-Black 1,393-bp deletion. In this case, the complete absence of β-globin gene expression seems to be compensated by an unusually high fetal globin gene expression (Hb F 96%). β-Globin haplotyping results were compatible with the propositus being homozygous for the Black 2 haplotype and for the absence of the XmnI polymorphism at −158 of Gγ-globin gene (−/−). Co-inheritance of genetic factors usually associated with high Hb F levels was not detected. Otherwise, the propositus is a heterozygote for the α-globin gene 3.7-kb deletion that is a beneficial modulating factor but not sufficient to explain this extremely mild phenotype. This unusual genotype/phenotype association is discussed in terms of the mechanisms underlying hemoglobin switching during development. Am. J. Hematol. 70:232–236, 2002. © 2002 Wiley-Liss, Inc.