Hyperhaemolysis in a pregnant woman with a homozygous β0-thalassemia mutation and two genetic modifiers

Introduction Patients with a homozygous beta(0)-thalassemia mutation usually have a transfusion-dependent beta-thalassemia major phenotype. However, some beta-thalassemia patients present with a relatively mild and even normal phenotype and always have a high level of Hb F induced by genetic modifiers. Methods In this study, we identified a homozygous beta(0)-thalassemia mutation (HBB: c.126_129delCTTT) in a 36-year-old pregnant woman. She had not presented any clinical symptoms of beta-thalassemia since birth. To investigate her unexpected mild phenotype, known genetic modifiers that ameliorate the severity of beta-thalassemia were analysed. Besides, we described the haematological changes during pregnancy. Results Two genetic modifiers (a heterozygous KLF1: c.519_525dup mutation; and two homozygous HBS1L-MYB locus SNP variants: rs7776054 and rs9399137) were identified. However, she showed a gradually decreased level of Hb during pregnancy, and serious transfusion complication of hyperhaemolysis was induced and complicated the pregnancy. Conclusion This report is in accordance with previous findings that genetic modifiers can ameliorate the clinical severity of beta-thalassemia, even without obvious clinical symptoms in a prolonged steady state. However, the steady state can be disrupted during pregnancy. In addition, raising awareness of hyperhaemolysis among clinicians treating patients with thalassemia is necessary.