Hemoglobin H Disease and Mental Retardation

Abstract

Each of three families of northern European origin contains a mentally retarded son with hemoglobin H (Hb H) disease. One parent is a carrier of mild α-thalassemia and the other is normal, suggesting that this form of Hb H disease results from the interaction between an inherited defect of α-chain production on one member of the pair in chromosome 16 and a new mutation on the other. Restriction-enzyme analysis indicated that the new mutation was not the same in the three patients, and demonstrated at least two hitherto undescribed lesions involving the α-globin gene cluster. Unless the association between Hb H disease and mental retardation is fortuitous, the new mutations may also be related to the developmental changes in these children. Since the mutations only came to light because there was concurrent inheritance of an additional α-thalassemia determinant, this type of mutation of chromosome 16 may have been overlooked in other mentally retarded patients. (N Engl J Med. 1981; 305:607–12.)