Asymptomatic homozygous deletional beta(0)-thalassemia in an African individual

• Published in: American journal of hematology 2002-07, Vol.70 (3), p.232-236
• Main Authors: Faustino, Paula, Reis, Ana Batalha, Feliciano, Helena, Ferrão, Lénia, Pereira, Patrícia, Picanço, Isabel, Miranda, Armandina, Seixas, Teresa, Romão, Luísa, Júnior, Esmeraldina Correia, Lavinha, João
• Format: Article
• Language: English
• Subjects: Anemia; Asthenia; beta-Thalassemia - blood; beta-Thalassemia - complications; beta-Thalassemia - diagnosis; Blood Transfusion; Fetal Hemoglobin - analysis; Fever; Gene Deletion; Globins - genetics; Guinea-Bissau - ethnology; Haplotypes; HIV Infections - complications; HIV Infections - diagnosis; HIV-2; Homozygote; Humans; Male; Middle Aged; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Portugal; Splenomegaly; Tuberculosis - complications; Tuberculosis - diagnosis
• ISSN: 0361-8609
• DOI: 10.1002/ajh.10118

Homozygosity or compound heterozygosity for beta(0)-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 beta(0)-thalassemia. At the molecular level, this is the first description of homozygosity for the beta(0)-Black 1,393-bp deletion. In this case, the complete absence of beta-globin gene expression seems to be compensated by an unusually high fetal globin gene expression (Hb F 96%). Beta-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 (G)gamma-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 alpha-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.