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

INTRODUCTION

Patients with a homozygous β -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 β -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.