PB2416 LABORATORY INVESTIGATION OF HEMOGLOBINOPATHIES IN HUNGARY

Abstract

Background:About 7% of the world population is affected by genetic defects of the hemoglobin molecule, making hemoglobinopathies the number one monogenic disease. Hemoglobinopathies were most common historically in the Mediterranean region and in African and south East Asian populations, but with the increase in migration from the twentieth century they are present worldwide. In Hungary the most common hemoglobinopathy is beta thalassemia, but is not endemic. In the majority of cases, the patients carrying the disease have little or no clinical symptoms. Routine laboratory investigations show a microcytic anemia, but to confirm the diagnosis further laboratory investigations are needed.Aims:To investigate the frequency of the different beta thalassemia mutations in Hungary and to present an algorithm for the investigation of microcytic anemias.Methods:In the period 2005‐2018, overall 3666 patients were investigated with the possible diagnosis of beta thalassemia. In all cases venepuncture was performed, and EDTA anticoagulated blood was collected from the antebrachial vein. Hemoglobin analysis was carried out with a high‐performance liquid chromatography method on a Variant II analyzer (Bio‐Rad, Hercules, CA, USA), and HbA2 and HbF levels were recorded. From 1704 samples DNA was isolated and Sanger sequencing of the beta globin gene was performed on an ABI Prism 310 Genetic analyzer (Applied Biosystems, Foster City, CA, USA).Results:In 1470 cases (40%), we found elevated HbA2 and/or HbF levels. In 1704 cases Sanger sequencing was performed and in 804 patients we found a mutation in in the beta globin gene as a cause of beta thalassemia. In 4 cases, a mutation leading to hemoglobin variants with increased O2 affinity were identified. Janus Kinase 2 (JAK 2) gene exon 12 mutations were not present in these patients with altered O2 affinity, but elevated hemoglobin and erythrocyte counts were observed, in accordance with the genetic results.Summary/Conclusion:We suggest an algorithm for the investigation of microcytic anemias in regions where the disease is not endemic, along with a few examples from our laboratory. Hemoglobin analysis is important in disorders where beta thalassemia might be suspected like hemolytic anemia, drug induced anemia and hydrops foetalis.