185: Recurrent Hemoglobin H hydrops Caused by a Compound Heterozygosity of HBA2: c.* 93_* 94delAA and ɑ0- thalassemia (-- SEA)

Abstract

We report Hb H hydrops fetalis resulting from non-deletional ɑ-thalassemia mutations, a polyadenylation (polyA) mutation (AATAAA → AATA--) of the ɑ2 globin gene (HBA2: c.*93_*94delAA), and ɑ0-thalassemia (--SEA) in 2 subsequent pregnancies from a Thai family living in Nakhon Pathom. Case Report In the first pregnancy, a 20 years old woman, GA 28+4 weeks, was referred to our hospital due to fetal cardiomegaly, marked anemia and pericardial effusion. She was ɑ0-thalassemia carrier (--SEA/ɑɑ), but her husband who had low mean cell volume (MCV) of 74 fL was negative for common ɑ-thalassemia mutation test. Therefore, they were not identified as a couple at risk for Hb Bart’s hydrops fetalis (--/--). Intrauterine transfusion (IUT), Hb typing, and complete ɑ-globin gene analysis were performed. The results showed that this fetus carried this rare ɑ globin genotype (--SEA/ɑPAɑ). The baby boy was born at 34+6 weeks, and subsequently died at 2 days of life owing to severe hydropic features and multiple organ failure. In the second pregnancy, the mother was detected with fetal cardiomegaly, pericardial effusion and marked fetal anemia at 30+1 weeks. We performed a fetal blood sampling and demonstrated a high level of Hb Bart (70.6%) and confirmed the same ɑ globin genotype again. Due to the grave prognosis of this genetic interaction, the couple decided for a termination of pregnancy rather than IUT, and our postmortem study revealed a full-blown hydrops fetalis in this female stillborn baby. Although recent publications have revealed a variety of clinical severity associated with this polyA mutation, varying from mild non-transfusion dependent to transfusion dependent, to the best of our knowledge, this is for the first time that this polyA mutation is associated with Hb H hydrops. Our probands were far more severe than those reported earlier even though they all had identical genotype, suggesting that there would be additional genetic and/or epigenetic determinants that might supersede or further deteriorating the clinical severity leading to hydropic development.