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.

Single Nucleotide Polymorphisms in XMN1-HBG2, HBS1L-MYB, and BCL11A and Their Relation to High Fetal Hemoglobin Levels That Alleviate Anemia

“…HBS1L-MYB is also a main regulator of erythropoiesis, and its expression may improve anemia in patients who have renal failure with the presence of rs7776054 and rs6650371 SNPs [ 73 ]. Both SNPs are significantly associated with high HbF levels that may ameliorate SCD and anemia in pregnant women [ 50 , 74 ].…”