Evaluation of Alpha-Thalassemia Mutations in Cases with Hypochromic Microcytic Anemia: The Istanbul Perspective

Objective: Alpha thalassemia syndromes are caused by mutations on one or more of the four a-globin genes. Mutations could be either more commonly deletional or non-deletional. As some deletions (3.7 and 4.2) cause alpha(+)-thalassemia, some cause (-20.5, MED, THAI, FIL) alpha(0)-thalassemia. The aim of this study was to determine alpha thalassemia mutations in patients with unsolved hypochromic microcytic anemia and to evaluate types of mutations. Material and Methods: Two hundred six patients with hypochromic microcytic anemia were evaluated for alpha thalassemia. A venous blood sample of 2 mL was drawn from each patient for DNA isolation. The samples were investigated for alpha-thalassemia mutations by using the Vienna Lab alpha-Globlin StripAssay TM commercial kit. Results: Fourteen different mutations were determined in 95 (46.1%) patients. The most common mutation was the 3.7 single gene deletion and was found in 37 patients (n=37/95, 39%). Others common mutations were the 20.5 kb double gene deletion (n=20 patients, 21%), MED double gene deletion (n=17 patients, 17.9%), alpha 2 IVS1 (n=10 patients, 10.5%), alpha 2 cd142 Hb Koya Dora (n=6 patients, 6.3%), alpha 2 polyAl (Saudi type) (n=6 patients, 6.3%), 4.2 single gene deletion (n=4 patients, 4.2%), alpha l cd14 (n=2 patients, 2.1%), and-FIL mutation (n=2 patients 2.1%), respectively. Hb Adana, Hb Icaria, alpha 2 init cd and alpha 2 polyA2 (Turkish type) were found in 1% of the patients (n=1). Seven patients (7.4%) had alpha-thalassemia triplication. In our study, three mutations (Hb Icaria, alpha l cd14, alpha 2 init.cd) were determined firstly in Turkey. Seven mutations (-SEA,-THAI, Hb Constant Spring, alpha 2 cd19, alpha 2 cd59, alpha 2 cd125, Hb Pakse) were not determined in this study. Conclusion: Alpha thalassemia should be considered in the differential diagnosis of hypochromic microcytic anemia especially in cases without iron deficiency and (beta-thalassemia carrier state. Genetic testing should be performed for the suspicious cases. We also recommend that a national database with all mutations in Turkey should be created to screen the alpha thalassemia cost-effectively.