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

Abstract

Introduction: Patients with a homozygous β0-thalassemia mutation usually have a transfusion-dependent β-thalassemia major phenotype. However, some β-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 β0-thalassemia mutation (HBB: c.126_129delCTTT) in a 36-year-old pregnant woman. She had not presented any clinical symptoms of β-thalassemia since birth. To investigate her unexpected mild phenotype, known genetic modifiers that ameliorate the severity of β-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 β-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.