Hemoglobin Bart's fetalis syndrome

Hemoglobin Bart's hydrops fetalis syndrome (also known as Hb Bart's hydrops fetalis, alpha-thalassemia major, or homozygous alpha-zero thalassemia) is the most severe form of alpha-thalassemia, caused by the deletion or inactivation of all four alpha-globin genes (HBA1 and HBA2) on chromosome 16. Without functional alpha-globin chains, the fetus cannot produce normal fetal hemoglobin (HbF) or adult hemoglobin (HbA). Instead, excess gamma-globin chains form gamma-4 tetramers known as hemoglobin Bart's (Hb Bart's), which has an extremely high oxygen affinity and is unable to effectively deliver oxygen to tissues, resulting in severe tissue hypoxia. The condition typically presents during the second or third trimester of pregnancy with hydrops fetalis — massive generalized edema, severe anemia, hepatosplenomegaly, and extramedullary hematopoiesis. Affected fetuses usually develop cardiomegaly, pleural and pericardial effusions, and ascites. The placenta is characteristically large and edematous. Without intervention, the condition is almost invariably fatal, with most affected fetuses dying in utero or shortly after birth. Mothers carrying affected fetuses are at significant risk of serious obstetric complications, including preeclampsia (toxemia of pregnancy), antepartum hemorrhage, and polyhydramnios or oligohydramnios. Hemoglobin Bart's hydrops fetalis syndrome is most prevalent in Southeast Asian and southern Chinese populations where the Southeast Asian (--SEA) alpha-zero thalassemia deletion is common. Prenatal diagnosis through chorionic villus sampling or amniocentesis is available for at-risk couples. In rare cases, intrauterine transfusions beginning in the second trimester followed by postnatal chronic transfusion therapy and ultimately hematopoietic stem cell transplantation have allowed survival of affected individuals, though long-term outcomes remain guarded and survivors may have significant developmental and medical complications. Genetic counseling is essential for carrier couples.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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