What characterizes alpha-thalassemia major (Hb Barts)?

Alpha-thalassemia major, also known as Hb Barts hydrops fetalis, is characterized by the complete absence of alpha globin chain production due to four gene deletions. In the context of human genetics, individuals typically have four alpha globin genes (two on each chromosome 16). When all four genes are deleted, the body is unable to produce any functional alpha globin chains, leading to severe anemia and a lack of normal hemoglobin formation, primarily resulting in the formation of abnormal hemoglobin such as Hemoglobin Barts, which is composed entirely of gamma chains.

This condition is incompatible with life, resulting in severe fetal hydrops and ultimately stillbirth or neonatal death. The severity of the condition arises from the critical role that alpha globin plays in forming hemoglobin and ensuring adequate oxygen transport in the body. In contrast to the other options, which represent various combinations of normal or missing genes, only the complete absence of all four genes leads to the profound pathology that defines alpha-thalassemia major.