Co-Inheritance of α-thalassemia gene mutation in patients with sickle cell Disease: Impact on clinical and hematological variables

Abstract

Background: Sickle cell disease (SCD) is a monogenic, phenotypically highly variable disease with multisystem pathology. The phenotypic heterogeneity of SCD is attributed to environmental and genetic factors such as fetal hemoglobin and co-inheritance of α-thalassemia.

Objectives: To look for different types of α-thalassemia gene mutations among SCD patients and evaluate the influence of the co-inheritance of α-thalassemia on clinical and hematological variables.

Methods: This cross-sectional analytical study included 765 SCD patients, and 150 patients (with low mean corpuscular volume (MCV), low mean corpuscular hemoglobin (MCH) and normal serum ferritin levels) were tested for α-thalassemia gene mutations. Multiplex PCR and reverse hybridization and sequencing for both α genes using the Vienna Lab Strip Assay PCR study were performed using conventional PCR technology.

Results: Out of 150 patients tested for α-thalassemia gene mutations, 141 patients were found to have one or more of the mutational types, representing 18.4% of all studied SCD patients. The most common mutations found were the -^3.7 deletion (76.6%), followed by the -^4.2 deletion (12.1%), mutant α2^polyA-1 (Saudi type) (9.2%), and --^MED double gene deletion (7.8%). Acute painful episodes did not differ significantly in sickle cell anemia (SCA) patients with or without α-thalassemia, although the co-inheritance of α-thalassemia has a protective role against many disease-related complications. However, this role was not observed with other types of SCD. The means of red blood cell count, hemoglobin, and hematocrit were significantly higher, while the MCV, MCH, reticulocyte count, and hemoglobin A2 percentage were significantly lower in patients with α-thalassemia gene mutations than in those without α-thalassemia gene mutations (P < 0.05).

Conclusions: The co-inheritance of α-thalassemia and SCA confers protection against many disease-related complications and is associated with improved hematological indices. However, this protection was not noticed in patients with other types of SCD.

Keywords: mutation; sickle cell disease; α-thalassemia.