PB2413 HAEMOGLOBIN AGHIA SOPHIA (HBA1:C.187_189DELGTG) IN NORTHERN GREECE. IMPLICATIONS IN CLINICAL PHENOTYPE OF HBH

Background: Alpha‐thalassaemia is inherited as an autosomal recessive disorder characterised by a microcytic hypochromic anaemia, and the clinical phenotype varies from almost asymptomatic to a lethal haemolytic anaemia. It is probably the most common monogenic gene disorder in the world. Several mutations have been described that can affect globin gene expression in any step and many of those mutations are rare causes of alpha thalassaemia. Aims: 28 patients have been diagnosed with Hb H disease (14 males and 14 females) from 1986 to 2019 at the regions of Central and Western Macedonia in Northern Greece with a population of around 2.5 million. The most prevalent genotype was the ‐α 3.7/—med, (5 cases), 2 cases of –α 3,7/‐α5,2, 1 case of –med/αPoly A, 1 case of –α 3,7/Hb Adana and 1 case of Hb Aghia Sophia/‐‐med. The phenotype suggests that HbH disease in Greece has in general a moderate presentation. The molecular characterization of the patients with Hb H disease is useful for the prediction of the clinical outcome and the genetic counselling of the couples at risk. Methods: Hb Aghia Sophia carriers are asymptomatic with normal or nearly normal Hb levels and red cell indices similar to α+ thalassaemia carrier as it was shown in 2 members of a family that this mutation was also detected in our region. Haemoglobin (Hb) Aghia Sophia in interaction with deletional α‐thalassaemia mutations leads to HbH. We report a case of Hb Aghia Sophia with co‐inheritance with the a‐thalassaemia – med deletion, a rare double heterozygosity case. Results: The case presented, concerns a 40 year old woman followed in our Thalassemia Clinic who was diagnosed at the age of 8 with Hb H. At diagnosis, totally incidental findings were compatible with a typical phenotype of Hb H, anaemia being mild and growth not having been impaired. As a girl, she retained a mild hypochromic microcytic anaemia until the age of 10 that a splenectomy was decided due to marked splenomegaly and anemia. During the following years her hemoglobin was maintained around 8gr/dl and she had normal growth. At the age of 35 she had an abortion. She was transfused each month during the next two pregnancies. Lately she was complaining for fatigue and her hemoglobin value was 7gr/dl. The investigation of hemoglobin deterioration did not reveal any significant cause. Bone marrow aspiration showed increased erythroid hyperplasia. Molecular examination revealed Aghia Sophia with co‐inheritance with the a‐thalassaemia – med deletion. As she denied transfusion, erythropoietin therapy was started with good results maintaining Hb level to 9gr/dl. Additionally, she receives deferasirox due to iron overload. Summary/Conclusion: The co‐inheritance of Hb Aghia Sophia with –med, is extremely rare and the severity is due to the interaction of a hyper unstable mutant of the a1 gene with an α0‐thal determinant. Hb Aghia Sophia causes instability to the polypeptide chain and is rapidly catabolized. Long follow‐up of such rare cases is necessary in order to gain as much information as possible, so as to offer the best management to the patients and the most accurate counseling to their families.