Two Cases of Sickle Cell Disease

By JAMES V. NEEL, PH.D., M.D., HARVEY A. ITANO, PH.D., M.D., AND JOHN S. LAWRENCE, M.D. I N RECENT YEARS our knowledge of the etiology of sickle cell disease has increased considerably. As a rule, both parents of a child with this disease show the sickle cell trait. This has led to the hypothesis that usually sickle cell disease is due to homozygosity for a gene which, when heterozygous, results only in the sickle cell trait . ‘ Occasionally, however, families are encountered in which the blood of oniy one of the parents of a child with clinical sickle cell disease can be induced to sickle. The study of such families has thus far resulted in the recognition of 3 other genetic types of sickle cell disease. In each of these 3 other types, the nonsickling parent is heterozygous for a gene responsible for another hematologic abnormality. The children who develop sickle cell disease in these families receive the gene responsible for the sickling phenomenon from one parent and 1 of the 3 other genes mentioned above from the other parent. The 3 other genes in question are: 1) the gene responsible for thalassemia, 6 2) the gene responsible for hemoglobin-c (hemoglobin-III),78 and 3) the gene responsible for hemoglobin-d.9 By now, approximately 18 families have been described in Italy, South America, and the United States in which sickle cell disease was presumably due to the first of the 3 less common mechanisms mentioned above, i.e., heterozygosity for both the sickle cell and the thalassemia genes.56’ ‘#{176}“ It is the purpose of the present report to describe still another such family. The justification for so doing is that the bloods of the 2 presumed “double heterozygotes” in this family have been subjected both to electrophoretic and alkaline denaturation studies, with results of some theoretic interest.