A combination of two novel alpha globin variants Hb Bridlington (HBA1) and Hb Taybe (HBA2) resulting in severe hemolysis, pulmonary hypertension, and death.

ABSTRACT

OBJECTIVE AND IMPORTANCE To describe two novel hemoglobin mutations that resulted in an unstable hemoglobin with a severe hemolytic phenotype. CLINICAL PRESENTATION A patient with an unstable hemoglobin and chronic hemolysis underwent splenectomy at age 15, subsequently developing chronic thrombo-embolic pulmonary hypertension at age 27 that was ultimately fatal. INTERVENTION DNA sequencing of the alpha globin gene revealed heterozygous inheritance of Hb Taybe, arising from a novel mutation in the HBA2 gene and Hb Bridlington, a novel HBA1 mutation. Greater disease severity is predicted by the position of the Hb Taybe mutation on the HBA2 gene (which transcribes more globin than the HBA1 gene). CONCLUSION: Splenectomy was not clearly beneficial and may have contributed to the development of pulmonary hypertension. The case favors a cautious approach when considering splenectomy for patients with Hb Taybe.