Diagnostic difficulties of carrier state in thalassemia syndromes for couple consultation and proposal of diagnostic points

Although, it is for several years (at least 15 years) that couples are tested for carrier state of thalassemia minor, there are still diagnostic problems due to vast genetic mutations. It is to mention that currently more than 200 different mutations that lead to &beta-thalassemia are known and in some cases the mutation is so mild that routine tests are not able to diagnose any abnormalities. These mild mutations are frequently diagnosed when a newborn with thalassemia intermedia or HbH disease is born. We have gathered diagnostic points and ideas for better diagnosis of carrier satates during the past 15 years. Cases of minor &beta-thalassemia with normal indices and normal HbA2, and also cases with thalassemic indices and normal HbA2 and also cases with normal indices and high HbA2 reflect genetic heterogenecity of thalassemia. It may be necessary to include determination of globin chain synthesis ratio in addition to routine CBC and HbA2 level for definite diagnosis of carrier states.