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

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.