A 7-month-old child with failure to thrive is found to have a hemoglobin of 4.4 g/dL. The peripheral smear shows very small red cells with marked pallor. It is determined that the child has very low levels of hemoglobin A, with elevated fractions of hemoglobin A2 and hemoglobin F. Which of the following underlying mechanisms is most likely related to the observed findings?
This child most likely has b+ thalassemia, an autosomal recessive disease that, in the homozygous state, produces defects in the transcription, processing, or translation of b globin mRNA. The predominant hemoglobin switches from HbF (a2g2) to HbA (a2b2) at about 6 months of age, at which point these children become markedly anemic because of their inability to synthesize the b globin chain. The anemia of b thalassemia is microcytic and hypochromic with anisocytosis. Amino acid substitutions in b globin lead to hemoglobinopathies, of which sickle cell anemia is the archetype. Homozygotes with these hemoglobin variants do not produce any HbA, but rather mutant types, such as HbS, HbC and HbM. Antibodies against fetal blood cells are generally produced by a mother who has been sensitized to fetal blood antigens by transfusion or a previous pregnancy. Such immune-mediated hemolysis leads to intrauterine anemia and hydrops fetalis. Cytoskeletal protein defects, such as spectrin deficiency causing hereditary spherocytosis, produce anemia and jaundice that are apparent at bih. The RBCs contain the normal types of hemoglobin.
Amino acid substitution on b globin
Antibody against fetal blood cells
Cytoskeletal protein defect
Insufficient production of b globin