Hemoglobin M equon β41 (C7) Phenylalanine → Tyrosine

A severe hemolytic crisis was observed in a 34-yr-old female of English- Irish extraction following a viral illness treated with acetaminophen. Heinz bodies and heat instability were present only during a transient hemolytic event. A challenge dose of acetaminophen caused no detectable hematologic abnormality. Structural studies of the hemoglobin during hemolysis and again after complete recovery localized the abnormality to tryptic peptide βTp-5, and automated sequencing of I125-labeled β chains indicated a replacement of phenylalanine (C7) β41 by tyrosine. Substitution of the next residue, phenylalanine (CD1) β42 by serine (Hb Hammersmith), has resulted in chronic severe Heinz body hemolytic anemia. The lack of chronic anemia in the present disorder may reflect the different relationships of β41 and β42 and/or the similarities in volume and hydrophobicity of tyrosine and phenylalanine. It is suggested that substitution of tyrosine for phenylalanine in Hb Mequon may disturb the critical environment around the heme group and render it susceptible to oxidative denaturation in the presence of infections and/or drugs.