Prenatal presentation of fetal anemia associated with εγδβ -thalassemia: two new cases

ورقة مؤتمر

2013

εγδβ-thalassemia is rare hematological disease caused by either a deletion of the beta-globin gene cluster, or deletion of the upstream β locus control region (LCR). It results in a phenotype of beta-thalassemia trait in adulthood. In the fetal and newborn period, the phenotype can range from self-limiting anemia to life threatening anemia requiring intra-uterine transfusions. Of the 30 εγδβ-thalassemia deletions reported so far, only 4 have been associated with severe congenital anemia requiring intervention or intrauterine transfusion. Here, we report the clinical course and molecular characterization of two new cases. Case 1 -A 26 year G1P0, Filipino (Southeast Asian) who presented at 194 weeks gestational age with polyhydramnios, fetal pericardial effusion and thickened myocardium. Fetal karyotype was normal. Cordocentesis showed a fetal hemoglobin of 30g/L, which required two intra-uterine transfusions. Delivery was induced at 36 weeks of gestation. Cord blood hemoglobin was 150g/L. Hemoglobin levels improved slowly (Hb at 9 months 96g/dl) and the patient did not require further blood transfusion. Alpha and Beta thalassemia molecular genetic testing was normal. Microarray analysis (Affymetrix Cytoscan HD) revealed a deletion of 54 kb encompassing the β LCR, HBE, HBG1 and HBG2 genes. The deletion was confirmed by FISH and shown to be maternally inherited. Case 2- A 42 years G2T1L1, Caucasian (Irish/Scottish) who presented at 333 weeks gestational age with polyhydramnios, umbilical cord cyst, thick placenta (7.8cm) and elevated MCA peak systolic velocity (94cm/sec). Patient was delivered by cesarean section at 335 weeks because of fetal hydrops. Cord blood hemoglobin was 49g/L, and multiple blood transfusions were needed over a 6 months period. Microarray analysis showed a deletion of 771 kb of the entire beta-globin gene cluster. The deletion was shown to be inherited from the father who had no prior history of anemia. Detailed family history however revealed a paternal aunt previously diagnosed with εγδβ-thalassemia 24 years ago and was reported as the >185 kb Canadian deletion (Diaz-Chico, 1988). In conclusion, we report the first εγδβ-thalassemia deletion diagnosed in a patient of South Asian ethnicity and present evidence of the inter-individual variation in the clinical presentation between carriers of the same deletion. In addition, we show that microarray can be a valuable tool to diagnose these deletions.

• موقع المؤتمر: Boston, Massachusetts
• اسم المؤتمر: The American Society of Human Genetics (ASHG) Annual Meeting