Dental Bone Changes Occurring in Sickle-Cell Diseases and Abnormal Hemoglobin Traits

Abstract

Since the discovery by Pauling and his co-workers of the abnormal hemoglobin associated with sickling of the erythrocytes (1), and by others of still different hemoglobin abnormalities, it has become possible to make a precise genetic diagnosis of a variety of congenital hemolytic disorders. By use of relatively simple technics of electrophoresis of hemoglobin, the presence of sickle hemoglobin (S), hemoglobin C (2), hemoglobin D (3), hemoglobin E (4), and hemoglobin G (5) can be detected and easily differentiated from the normal. Clinical experience with patients having these abnormal hemoglobins suggests that each responsible gene acts as a simple mendelian dominant and that each is probably allelic with the determinant for normal hemoglobin. In such circumstances one would expect that an individual might inherit any combination of two of these abnormal genes and that the clinical manifestations of such inheritance would be represented by a modified expression of each. Examples of some of the possible combinations have been encountered and various observations suggest that the clinical pattern of each such genetic disorder is indeed determined by the features of the combined genes. Those abnormal hemoglobin states which have been recognized are sickle-cell trait, hemoglobin C, D, E, and G traits, homozygous sickle inheritance (sickle-cell anemia), homozygous hemoglobin C inheritance (hemoglobin C disease) (6), homozygous hemoglobin E disease (7), and combinations of sickle and hemoglobin C, sickle and hemoglobin D, sickle and hemoglobin E, and sickle and hemoglobin G. Suggested nomenclature (8) for these disorders is given in Table I. Gene frequencies for S and C hemoglobins are relatively high in the Negro population. Hemoglobins D, E, and G, on the other hand, are apparently quite rare. Still other hemolytic disorders may result from the inheritance of a single gene for an abnormal hemoglobin and a determinant for other red-cell abnormalities, Examples of such combinations that have been encountered are sickle-cell thalassemia (9), sickle-cell hereditary sphero-cytosis (10), and hemoglobin-C thalassemia (11). Despite the number of these often interrelated congenital hemolytic states, a precise genetic diagnosis can often be easily made by the use of filter paper electrophoresis of the hemoglobin and examination of the blood smear. On clinical grounds alone, even the differentiation between sickle-cell trait and sickle-cell anemia may at times be exceedingly difficult. Establishing a precise diagnosis becomes important when it is realized that the prognosis of the various genetic disorders differs greatly. It now seems clear that sickle-cell anemia, which results from homozygosity for the sickling character, is almost invariably a severe hemolytic disorder. On the other hand, the variant forms of sicklemia are frequently mild and may have no obvious clinical expression.