A combination of the -α3.7 and --MEDII alleles causing hemoglobin H disease in a Brazilian patient

Alpha-thalassemia is a hereditary disease with a worldwide distribution characterized by reduced or absent synthesis of hemoglobin chains. Deletions involving the globin genes, which are duplicated ( 2 and 1) and located in the cluster (16p13.3), are the most common causes of the disease and account for over 80% of cases. Loss of a functional gene in the haploid genome results in +-thalassemia, which can occur in a heterozygous (/ ) or homozygous(/) state, while loss of both genes results in 0-thalassemia,which can also occur in a heterozygous (–/ ) or homozygous (–/–) state. A fifth thalassemic genotype is the result of the combination of both the 0 and + alleles (/–). While the first three genotypes are associated with minimal hematological changes and the fourth results in hemoglobin (Hb) Bart’s hydrops fetalis with intrauterine or neonatal death, the double heterozygous 0/ + (/–) state leads to Hb H disease. This latter is characterized by unstable chain tetramers ( 4), causing chronic, moderate to severe hemolytic anemia with microcytosis, hypochromia, jaundice and hepatosplenomegaly.1,2