Homozygosity for the Severe β⁺-Thalassemia Mutation [IVS-I-5 (G>C)] Causes the Phenotype of Thalassemia Trait: An Extremely Rare Presentation

Abstract

The thalassemias are the most common single gene disorder known to mankind. The phenotype of thalassemia depends upon the underlying gene defect in addition to many modulating factors. As the literature describes, inheritance of a β⁰ genotype in the homozygous state results in the development of β-thalassemia (β-thal) major with key clinical features being transfusion dependency, physical abnormalities and iron overload. IVS-1-5 (G>C) is the severe β⁺ allele whose homozygosity results in severe β-thal. We describe a patient who was asymptomatic until screened and was found to have mild anemia. Detailed analysis revealed the presence of the IVS-I-5 mutation in a homozygous state that was unlikely to present as a transfusion independent state. The study of such cases emphasizes the complexity of genetic interactions that underlie the phenotype of β-thal and highlight the importance of the regulation of Hb F production in β-thal syndromes. Simultaneous inheritance of some loci that modulate Hb F levels probably causes high levels of total hemoglobin (Hb) and to be transfusion independent.

• β-Thalassemia (β-thal)
• IVS-I-5 (G>C)
• Hb F