Difficulties in the diagnosis of Hb S/Beta thalassemia: Really a mild disease?

Abstract

OBJECTIVE: HbS/β cases having clinical, hematologic and electrophoretic similarities cannot be sufficiently distinguished from sickle cell anemia cases, and are misdiagnosed as sickle cell anemia. This study will investigate the congruence between the HPLC thalassemia scanning tests and the laboratory findings in comparison with the DNA sequence analysis results of the patients diagnosed with SCA between 2016 and 2020. This study also aims to indicate the current status to accurately diagnose sickle cell anemia and HbS/β in the light of hematologic, electrophoretic and molecular studies.

MATERIAL METHOD: Fourteen patients who were diagnosed with SCA in hospitals at different cities in Turkey and followed by the Thalassemia Diagnosis, Treatment and Research Center, Muğla Sıtkı Koçman University were included in this retrospective study. The socio demographic characteristics, hemogram, hemoglobin variant analysis results and DNA chain analysis results of the patients were taken from the database of the center and then examined. The informed consents were taken from the patients. The patients were administered a survey containing questions about transfusion history and diagnostic awareness.

The Beta-Thalassemia mutations were analyzed using DNA sequencer (Dade Behring, Germany) based on the Sanger method.

RESULTS: According to the DNA sequence analysis results of these patients diagnosed with SCA in hospitals in different cities of Turkey: Of 14 patients, 8 had Hb S/β⁰ and Hb S/β⁺ and one had Hb S carrier, and one had Hb-O, and three had SCA. The patient with HbS carrier status also contains three additional mutations all of which are heterozygous. We discovered that although two of three mutations, which are c.315+16G>C and c.316-185C>T, are previously reported as benign, at least one of the two mentioned mutations, when combined with Hb S, causes transfusion-dependent Hb S/β.

CONCLUSION: Briefly, HbSS and HbS/β thalassemia genotypes cannot be definitely characterized by electrophoretic and hematologic data, resulting in misdiagnosis. c.315+16G>C and c.316-185C>T, are previously reported as benign, at least one of the two mentioned mutations, when combined with Hb S, causes transfusion-dependent Hb S/β.

 In undeveloped or some developing countries, molecular diagnosis methods and genetic analyses cannot be used. If mutation analyses could be performed, then such differential diagnosis errors would reduce. However, if mutation analysis cannot be performed, other methods such as HPLC, capillary electrophoresis absolutely be sought to have insight into the parental carriage status.